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Supplement/Drug Name indicate using to and from your chosen support team members who you share this
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2 Deoxyglucose -
20-40% caloric restriction -
3-Bromopyruvate -
Acetominophen -
Acetyl-l-carnitine -
Amiloride (Midamor) -
Amla -
Andrographolide -
Anthocyanins -
Apigenin -
Arabinoxylose -
Artemisinen/Artusenate -
Aspirin (or willow bark) -
Ashwagandha -
Atovaquone -
Astragalus -
Auranofin -
Azithromycin -
Baicalein -
B17 (Amygdalin) -
Berberine -
Beta 1,3-Glucan -
Beta Carotene -
Beta Hydroxybutyrate -
Beta-sitosterol -
Betulinic acid -
Bitter Melon -
Black Seed Oil (Nigella Sativa) -
Boswellia -
BPTES -
Bromelain -
Burdock (Arctigenin) -
Butcher's Broom -
Capsaicin -
Caffeic Acid - note: Caffeic Acid is not related to Caffeine
Carnisol -
Cat's Claw -
CBD (from Cannabis) -
Chitin -
Chlorella -
Choline -
Chromium -
Chrysin -
Cimetidine -
Cinnamon (not culinary) - *standardized to Cinnamaldehydes and phenolic compounds.
Citrate -
Citrus Bergamot -
Clemastine -
Colostrum -
Conjugated Linoleic Acid (CLA) - Warning: Not for HER2+
CoQ10 -
Cordyceps -
C-Statin -
Curcubitacin B -
Curcumin -
Cyclo-creatine Phosphate -
Cysteinase (PDAC) -
d-Mannose -
Dandelion
Danshen (Salvia Miltiorrhiza) -
Desloratidine -
DHEA -
Daidzin (soybean) -
Deferoxamine -
Dichloroacetate (DCA) -
Diet Low GI -
Diet Low Asparagine -
Diet Low Methionine/Cysteine -
Diet No Sugar, No Dairy -
DIM/I3C -
Dipyridamole -
Disulfiram -
Doxycycline -
Echinacea -
EGCG -
Ellagic acid -
Exercise -
Exercise (post-meal) -
Extra Virgin Olive Oil -
Fasting with Chemotherapy -
Fenbendazole -
Fenofibrate -
Fenugreek (Trigonelline) -
Fermented Wheat Germ Extract -
Feverfew -
Fisetin -
Flaxseed -
Flubendazole -
Folate (5-MTHF) -
Follistatin -
Fucoidan -
Fucoxanthin -
Garlic extract -
Genistein -
Ginger -
Gingko Biloba (Gingketin) -
Glucosamine Sulfate -
Grapeseed/skin extract -
Graviola -
Gynostemma -
Hari Taki -
HBOT -
Hesperetin -
Heteronemin -
High Dose Allicin -
Honokiol -
Hydroxychloroquine/Chloroquine -
Hydroxycitrate (Garcinia Cambogia) -
Hyperthermia -
Ibuprofen -
 Intermittent Fasting -
Iodine -
Intense exercise -
IP-6 -
Ipriflavone -
Itraconazole -
Ivermectin -
IV Vitamin C -
IV Curcumin -
IV Alpha Lipoic Acid -
Ivermectin -
Juglone (Black Walnut) -
Kaempferol -
Ketogenic Diet -
Ketotifen -
Lactoferrin (Apo form) - *Typical form of lactoferrin
Lactoferrin (Holo form) - *Not the form commonly found
LD Naltrexone -
Leflunomide -
Licorice root -
Liposomal Vitamin C -
Longer fasts -
Loratadine (Claritin) -
Low Dose Chemo -
Low Dose Insulin-Potentiated Chemo -
Luteolin -
Lumbrokinase -
Lycopene -
Magnesium -
Mebendazole -
Meditation, yoga, qigong etc -
Melatonin -
Metformin -
Methotrexate -
Mildronate -
Mistletoe -
Modified Citrus Pectin (MCP) -
Moringa -
MSM -
Mushrooms: Reishi, Coriolus -
Myomin -
Myricetin -
N-acetyl cysteine (NAC) -
Narigenin -
Nattokinase -
Neem -
Niclosamide -
Niacin (Nicotinamide) -
Niacin (Nicotinic acid) - *Flushing type
Nicotinamide Riboside -
Nifuroxide -
Nitazoxanide -
Noni -
Noscapine - *Found in over-the-counter cough medicines.
NSAID -
Olive Polyphenols -
Omega-3 EPA/DHA -
Omega-3 DHA -
Omega-6 GLA -
Omeprazole -
Oxygen Therapies -
Panax Ginseng -
Passiflora foetida -
Pau d'Arco (Taheebo) -
Pawpaw -
PEITC -
Phosphatidylcholine -
Phosphatidylethanolamine (PEA) -
Piperine -
Piperlongumine -
Polydatin -
Pomegranate -
Poria Cocos -
Probiotics -
Progesterone - Actually make let me make you a copy of my hard drive and share with you. Maybe that will work
Pro-Resolving Mediators -
Propranolol -
Pterostilbene -
Pyrvinium Pamoate -
Quercetin -
R-Alpha Lipoic Acid (no 'S' ) -
Rabdosia Rubescens -
Rapamycin -
Red Yeast Rice -
Reishi mushroom -
Resveratrol -
Rosmarinic acid -
RSL3 -
Salinomycin (Ironomycin) -
Schisandra -
Sea buckthorn oil -
Selenium -
Serine restriction -
Serrapeptase -
Shark Liver Oil -
Siberian Ginseng (Eleuthero) -
Silibinin/Silymarin/Milk Thistle -
Silica -
Sirasemine -
Sodium phenylbutyrate -
Sodium Selenite -
Solomons Seal -
Spatholobus suberectus -
Spermidine -
Sphingomyelin -
Statin -
Sulfasalazine -
Sulforaphane -
Superoxide Dismutase - *SOD1
Syrian Rhubarb -
Syrosingopine
Tamoxifen -
Taurine -
Tetrathiomolybdate (TM) -
THC (from cannabis) -
Thymosin -
Tinospora Cordifolia -
 Tocopherols -
Tocotrienols -
Tri-Methyl Glycine (TMG) -
Turkey Tail (Coriolus Versicolor) -
Ursolic Acid -
Valproic Acid -
Vitamin A -
Vitamin B6 -
Vitamin B12 (methylcobalamin) -
Vitamin C -
Vitamin D3 -
Wasabi -
Zinc -
Please note all other treatment therapies, supps and/or drugs you are currently taking that do not appear on the A-Z list above. Include dosage notes.
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Do not edit or delete these:

Indicate via 2 Input will fill Input will fill
Part 2 - Combinations matches item 1 automatically AND item2 automatically
Aspirin (or willow
Aspirin + Dipyridamole bark) - Dipyridamole -
Berberine + Aspirin Berberine - Aspirin (or willow bark) -
Curcumin + EGCG Curcumin - EGCG -
Curcumin + Ursolic Acid Curcumin - Ursolic Acid -
Metformin + Aspirin Metformin - Aspirin (or willow bark) -
NSAID + Statin NSAID - Statin -
NSAID + Tocotrienols NSAID - Tocotrienols -
Resveratrol + Ursolic Acid Resveratrol - Ursolic Acid -
Ursolic Acid + Aspirin Ursolic Acid - Aspirin (or willow bark) -
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YES taking
Considering
Suggested
1wk in 4
Cycling
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 Manipulate Signaling
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION: Normal cells depend on growth signaling of a tightly-regulated cell cycle to maintain balanced growth. Cancer cells
mutate to manipulate these signaling pathways to initiate growth and begin the process of creating an initial tumor and metastases.
Genetic analysis of a tumor or circulating tumor cells (CTCs) (Foundation One, CARIS, Guardant, RGCC) can reveal which pathways a
particular cancer is using. In the absence of tumor genetics, it's important to block all the signaling pathways listed for a particular
breast cancer subtype.
KEY: ER+HER2- includes ER+PR+HER2- and ER+PR-HER2-, TPBC includes ER+PR+HER2+ and ER+PR-HER2+, HER2-Enriched includes ER-
PR-HER2+ , and TNBC includes ER-PR-HER2-.
SPECIAL CONSIDERATIONS for ER+: Some substances may require further exploration as to their use in ER+ breast cancer (HER2+ or
HER2-). For more information, see ER+ Special Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.

Estrogen Signaling
Estrogen signalling is important for all ER+ breast cancers including TPBC. Improving P53 function important for ER+, and
sensitivity to aromatase inhibitors is regulated by the TP53 gene. read more
Please note that SOC oncology drugs are not included here. Some of these substances are meant as additions to standard therapies
and others possibly as replacements only under the guidance of an integrative doctor who is fully exploring hormonal metabolism
through testing.
ER+HER2-: Important for all
TPBC: Important for all. Important to concurrently block PI3K/Akt/mTOR to reduce resistance to estrogen-blocking therapy. There is
"cross-talk between Estrogen and HER2 signaling, which can lead to treatment resistance. CDK4/6 blocking drugs like Ibrance are
being studied in TPBC as a way to reduce resistance to endocrine therapies. Some HER2+ may not respond well to Tamoxifen if they
express HER4.

HER2-Enriched: Not applicable

TNBC: Not applicable
Substance Notes
- Apigenin *weak aromatase inhibitor
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Artemisinen/Artusenate
- Baicalein *Not a standalone therapy. Reduces Tamoxifen and AI resistance by blocking HIF-1.
- Betulinic acid *Improves effectiveness of Tamoxifen or Faslodex
- Bromelain *indirect via blocking MUC1 protein
- Burdock (Arctigenin) *synergy with Tamoxifen
- Chrysin *aromatase Inhibitor
- Danshen (Salvia Miltiorrhiza) binds to receptors, inhiibits ERa transcription activity
- DIM/I3C *improves effectiveness of Tamoxifen
- Flaxseed
- Hesperetin *weak aromatase inhibitor
- Iodine
- Melatonin *high dose, see notes
- Myomin *aromatase Inhibitor, minimal scientific evidence
- Olive Polyphenols *aromatase inhibitor, specifically oleuropein but not hydroxytyrosol
- Pau d'Arco (Taheebo)
- Progesterone *oral bioidentical, under doctor's supervision
- Selenium
- Sulforaphane
- Tocopherols *gamma and delta only
- Tocotrienols *activates ER-beta; should be dosed separately from tocopherols
- Vitamin D3 *blocks enzyme need to synthesize 27-hydroxycholesterol (27HC)
Hedgehog Signaling
Cancer cells mutate and use Hedgehog signaling to resist chemo and create metastases. Read more
ER+HER2-: Previously limited to TNBC but potentially important in Luminal B; Luminal A often become Luminal B when cancers
progress to Stage IV. Also plays a role in Tamoxifen resistance.
TPBC: Previously thought to be limited to TNBC but now being studied in HER2+ (Luminal B). Also plays a role in Tamoxifen
resistance.
HER2-Enriched: Previously thought to be limited to TNBC but now being studied in HER2-Enriched.
TNBC: One of the most important TNBC pathways to block. Inhibitors of Hedgehog/glioma-associated oncogene signaling inhibit
growth of TNBC cell lines.

Substance Notes
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Berberine
- Curcumin
- Itraconazole *Caution, strong CYP3A4 inhibitor
- Mebendazole
- Metformin
- Sulforaphane

Wnt/beta-catenin Signaling
Cancer cells mutate and use Wnt/beta signaling to resist chemo and create metastases. It is also important in the process
of cancer stem cells evolving into to mature cancer cells.
ER+HER2-: Common in ER+HER2- and plays a role in Tamoxifen and AI resistance.
TPBC: Important to block to avoid Herceptin (Kadcyla, Enhertu, or Tucanatib) resistance. Correlated with ER expression and involved
in Tamoxifen and AI resistance. Highest expresion of Wnt mutation in TPBC of all subtypes (see fig. 3 of ref).

HER2-Enriched: Important to block to avoid Herceptin (Kadcyla, Enhertu, or Tucanitib) resistance.

TNBC: One of the most important TNBC pathways to block as it regulates cancer stem cell (CSC) activity, promoting tumor
progression and distant metastasis via the protein Cadherin 11.

Substance Notes
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
Aspirin + Dipyridamole
- Atovaquone
- Baicalein
- Berberine
- Capsaicin
- Curcumin
- Dipyridamole
Echinacea
- EGCG
- Ginger
- Luteolin
- Melatonin
- Niclosamide
- NSAID
- Omega-3 DHA
- Olive Polyphenols *hydroxytyrosol
- Pomegranate
- Pyrvinium Pamoate
- Quercetin
- Reishi Mushroom
- Resveratrol
- Sulforaphane
- Tocotrienols
- Vitamin D3
Notch Signaling
Cancer cells mutate and use Notch signaling to resist chemo and create metastases. Notch signaling is up-regulated during
radiation therapy and allows the tumor create breast cancer stem cells.
ER+HER2-: Deregulated Notch signaling within the breast tumor and its tumor microenvironment (TME) is linked to poor clinical
outcomes in chemo and endocrine resistant breast cancer. Read more.
TPBC: Cooperates with other signaling pathways to upregulate HER2/neu and involved in Herceptin resistance as it increases NFkB.
Also plays a role in resistance to Tamoxifen and AIs. Read more.
HER2-Enriched: Cooperates with other signaling pathways to upregulate HER2/neu and involved in Herceptin resistance as it
increases NFkB.
TNBC: One of the most important TNBC pathways to block as it regulates TNBC mitochondrial activity, stimulates P13K/AKT
phosphorylation, oxidative metabolism and transcription of survival genes in PTEN wild-type TNBC cells. Found in more than one-third
of TNBC tumors (see fig. 3 of ref).

Substance Notes
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Curcumin
- Ginger
- Luteolin
- Niclosamide
- Pterostilbene
- Quercetin
- Resveratrol
- Sulforaphane
STAT3 Signaling
STAT3 signalling is initiated by IL-6, EGFR; STAT3 triggers TAMs,VEGF, HIF-1alpha, FGFR, nfKB. STAT3 activates
several genes important in immune system takeover, metastasis, angiogenesis, apoptosis, and resistance to chemo. Read
more STAT3 is important in brain metastases.
ER+HER2-: STAT3 activation is important in resistance to endocrine therapies. Increased IL6 expression upregulates STAT3 and
leads to decreased survival in ER+HER2- breast cancer.
TPBC: STAT3 activation is important in resistance to endocrine therapies and and is commonly overexpressed in HER2+. Blocking
STAT3 is important to reduce resistance to HER2+ targeted therapies.
HER2-Enriched: Commonly overexpressed in HER2+. Blocking STAT3 is important to limit resistance to HER2+ targeted therapies.

TNBC: One of the most important TNBC pathways to block as STAT3 is overexpressed and activated in TNBC and is highly related to
TNBC initiation, progression, metastasis and resistance to chemotherapy.

Substance Notes
- Apigenin
- Baicalein
- Betulinic acid
- Chrysin *aromatase Inhibitor
Curcumin + EGCG
Dandelion
- Danshen (Salvia Miltiorrhiza)
- Feverfew
- Fisetin
- Flubendazole
- Honokiol
- Ivermectin
- Luteolin
- Melatonin
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- MSM
- Niclosamide
- Nifuroxide
- Quercetin
- PEITC
- Reishi Mushroom
- Resveratrol
- Silibinin/Silymarin/Milk Thistle
- Sulforaphane
- Tocotrienols
 PI3K/Akt/mTOR Signaling (PTEN deletion)
An important signalling pathway for stem cell growth and longevity in normal cells that is highly stimulated by glucose and
insulin. Mutations lead to abnormal cell growth, loss of apoptosis, and resistance to chemotherapy and endocrine therapy.
Upregulated PI3K/AKT/mTOR signaling leads to increased glycolysis, glutaminolysis, fatty acid synthesis (FAS), and fatty
acid oxidation, all of which perpetuate cancer cell growth. PIK/Akt/mTor is upregulated by FAS (see Dysregulate
Metabolism) so it's important to block FAS as well. p53 mutations block therapies like Piqray that act on PI3K mutations so
it's important to improve p53 function along with any therapy intended to block PI3K (see Invade/Metastasize tab).
Read more
ER+HER2-: Upregulation of PI3K/Akt/mTOR is an important mechanism for developing resistance to CDK4/6 inhibitor drugs so
blocking this pathway is important when on these drugs. PI3K mutation is found in 62% of ER+HER2- breast cancers (see fig. 3 of ref)
and is responsible for the development of resistance to estrogen blocking therapy. This mutation can be tested in serum or tumor
tissue, and an oncology drug alpelisib is an approved treatment. When taking an estrogen blocking drug at any stage it is important to
block this pathway to reduce resistance.

HER2-Enriched: Loss of PTEN expression is correlated with Herceptin resistance and TKI resistance so any substance that blocks
PI3K/Akt/mTOR should help restore sensitivity to Herceptin, the Herceptin drug-conjugate drugs Kadcyla and Enhertu, and TKIs like
neratinib and tucatinib. Another study.
TPBC: Loss of PTEN expression is correlated with Herceptin resistance and TKI resistance so any substance that blocks
PI3K/Akt/mTOR should help restore sensitivity to Herceptin, the Herceptin drug-conjugate drugs Kadcyla and Enhertu, and TKIs like
neratinib and tucatinib. Another study. When taking aromatase inhibitors at any stage, it is important to block this pathway to reduce
resistance.

TNBC: One of the most important TNBC pathways to block, especially in BRCA1 mutations, found in more than half of TNBC tumors
(see fig 3 of ref.).More information about the PI3K/Akt/mTOR pathway in TNBC.

Substance Notes
- Andrographolide
- Apigenin
- Artemisinen/Artusenate
- Aspirin (or willow bark) *reduced breast cancer deaths shown for early-stage tumors not Stage 4.
- Baicalein
- Black Seed Oil (Nigella Sativa)
- Chrysin
- Citrate
- Curcumin
- Danshen (Salvia Miltiorrhiza)
- DIM/I3C
- EGCG
- Fisetin *may cause liver toxicity if taken for extended period
- Fucoidan
- Genistein
- Ginger
- Honokiol
- Ivermectin
- Luteolin
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
NSAID + Tocotrienols
- Olive Polyphenols *specifically hydroxytyrosol
- Poria Cocos *Especially with astragalus
- Propranolol
- Quercetin
- Rapamycin
- Resveratrol
- R-Alpha Lipoic Acid (no 'S' )
- Spatholobus suberectus
- Sulforaphane
- Tocotrienols
- Ursolic Acid
NF-kB Signaling
 NF-kB drives every one of the Hallmarks of Cancer. It is an Inflammatory factor activated by IL-6 (immune response) and
forms a signaling pathway with RANKL that is important in bone mets and endocrine therapy resistance. In bone mets,
upregulated IGF-1 and Akt lead to upregulated NFkB. NFkB also upregulates the CXCR4 axis, which is implicated in bone
mets. NFkB upregulates LOX, which contributes to brain mets, chemotherapy resistance, and endocrine therapy resistance.
NF-kB is very important to block with multiple substances as well as with an anti-inflammatory diet and lifestyle.

ER+HER2-: ER+ and NFkB together promote endocrine resistance, metastasis, and disease relapse. Endocrine therapy resistance
can come from upregulated NfKB-RANKL signaling.

TPBC: Resistance to Herceptin and related targeted therapies is created by upregulated NFkB signaling.
HER2-Enriched: Resistance to Herceptin and related targeted therapies is created by upregulated NFkB signaling.
TNBC: One of the most important TNBC pathways to block as NF-κB regulates the expression in TNBC cells and is involved in cell
adhesion, migration and proliferation. NF-κB inhibition decreases proliferation and invasiveness of TNBC cells.

Substance Notes
- Andrographolide
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Aspirin (or willow bark)
- Astragalus
- Baicalein
- Berberine
- Betulinic acid
- Black Seed Oil (Nigella Sativa)
- Bromelain
- Burdock (Arctigenin)
- Curcumin
- Danshen (Salvia Miltiorrhiza)
- Dipyridamole
- Doxycycline Do not take on an empty stomach
- EGCG
- Feverfew
- Fucoidan
- Fucoxanthin
- Genistein
- Ginger
- Gingko Biloba (Gingketin)
- Modified Citrus Pectin (MCP) *better in comination with Honokiol
- Lycopene *take with oil-based products such as Black Cumin Seed Oil or Omega-3
- Meditation, yoga, qigong etc
- Melatonin
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- MSM
- Olive Polyphenols *specifically oleuropein
- Omega-3 EPA/DHA
- Panax Ginseng
- Piperine
- Pomegranate
- Probiotics
- Propranolol
- Quercetin
- Reishi mushroom
- Resveratrol
- Sulforaphane
- Tocotrienols
- Turkey Tail (Coriolus Versicolor)
- Ursolic Acid
- Vitamin D3
AMPK Signaling (upregulate, not block)
Anything that downregulates mTOR upregulates AMPK and vice versa. Based on one cell line study, it may be important to
block FAO (see Generate Energy) directly or indirectly) if strongly upregulating AMPK with Metformin while on estrogen
blocking therapy. Effect not established in vivo, though a recent clinical trial showed no improvement in recurrence risk for
women using Metformin as an adjuvant therapy, except for a subset with HER2+ breast cancer.
ER+HER2-: AMPK activation decreases growth and increases apoptosis in estrogen-receptor positive breast cancer.

TPBC: AMPK activation has downstream effects on HER2/neu signaling by inhibiting mTOR, which is important in HER2+ breast
cancer.
HER2-Enriched: AMPK activation has downstream effects on HER2/neu signaling by inhibiting mTOR, which is important in HER2+
breast
TNBC:cancer.
Important in TNBC. AMPK activation decreases growth and increases apoptosis in triple negative breast cancer.

Substance Notes
- 20-40% Caloric restriction
- Anthocyanins
- Aspirin (or willow bark) *reduced breast cancer deaths shown for early-stage tumors not Stage 4.
- Berberine
- Curcumin
- EGCG
- Honokiol
- Intense exercise
- Ivermectin
- Metformin *Effects enhanced with addition of aspirin or beta blocker. Take a B12 supplement while on Metformin
- Olive Polyphenols *specifically hydroxytyrosol
- R-Alpha Lipoic Acid (no 'S' )
EGFR Signaling
Associated with lung mets and brain mets; triggers PI3KAkt, which activates c-Myc and the pentose phosphate and
glycolysis and glutamine metabolism . Also activates STAT3, which leads to resistance to oncology drugs.
ER+HER2-: Prolonged CDK4 blockade (i.e., with Ibrance, Verzenio, Kisquali) as well as Aromatase Inhibitors can promote over-
expression of EGFR, which can leads to CDK4/6 drug resistance and reduced sensitivity to Tamoxifen and AIs.
TPBC: Tyrosine kinase inhibitor drugs (TKIs) are available for HER2+ tumors that over-express EGFR including Lapatinib and
Neratinib. The natural substances that inhibit EGFR may potentiate the action of these drugs. Aromatase Inhibitors can upregulate
expression of EGFR, which can lead to therapy resistance.

HER2-Enriched: Tyrosine kinase inhibitor drugs (TKIs) are available for HER2+ tumors that over-express EGFR including Lapatinib
and Neratinib.The natural substances that inhibit EGFR may potentiate the action of these drugs.
TNBC: More often expressed in TNBC than other subtypes. EGFR silencing inhibits TNBC cell proliferation and increases apoptosis
through the suppression of STAT3. EGFR inhibitor drugs have been unsuccessful in TNBC tumors that overexpress EGFR, and this is
thought to be related to the upregulation of hormonally upregulated neu-associated kinase (HUNK), which may be a target for new
drugs.The natural substances that inhibit EGFR are particularly important for TNBC along with conventional therapy.

Substance Notes
- Berberine
- Bromelain
- Curcumin
- EGCG
- Fisetin *may cause liver toxicity if taken for extended period
- Grapeseed/skin extract
- Graviola
- Honokiol
- Luteolin
- Melatonin
- Omega-3 DHA
- PEITC
- Quercetin
- Silibinin/Silymarin/Milk Thistle
Ursolic Acid + Aspirin
HER2/neu Signaling
HER2 is a member of the EGFR family of overexpressed growth signaling, which also includes HER1, HER3, and HER4.
The listed supplements downregulate HER2/neu expression and improve effectiveness of drugs used in HER2+ breast
cancer including Herceptin, Perjeta, TKIs (Lapatinib, Tukysa, and Neratinib), and Herceptin drug conjugates (Kadcyla and
Enhertu).
ER+HER2-: N/A though a small percentage of tumors may be heterogenous and express HER2/neu in some cells even if HER2- in
initial pathology.
TPBC: Most important pathway in this subtype. CDK4/6 inhibitor drugs may overcome resistance to anti- HER2 therapies in TPBC;
clinical trials are available. Aromatase inhibitors can upregulate expression of HER2/neu, which can lead to therapy resistance
HER2-Enriched: Most important pathway in this subtype.

TNBC: N/A
Substance Notes
- Apigenin
- Artemisinen/Artusenate
- Berberine
- Beta-sitosterol
- Bromelain
- Capsaicin
- CBD (from Cannabis)
- Hydroxychloroquine/Chloroquine *May not be advised with some targeted therapies; consult oncology pharmacist
- Curcumin
- Cyclo-creatine Phosphate
- Danshen (Salvia Miltiorrhiza)
- Omega-3 DHA
- DIM/I3C
- Doxycycline
- EGCG
- Fisetin *may cause liver toxicity if taken for extended period
- Flaxseed *Effects due to ALA to DHA conversion
- Flubendazole
- Genistein
- Hesperetin
- Ivermectin *Increases effectiveness of HER2-targeted drugs
- Melatonin
- Metformin *may block macropincytosis in HER2+ and reduce resistance to therapy
- Mistletoe
- Moringa
- MSM
- N-acetyl cysteine (NAC)
- Narigenin
- Olive Polyphenols *specifically oleanolic acid
- Omega-3 EPA/DHA
- Omega-6 GLA
- PEITC
- Pomegranate
- Propranolol *used concurrently with Metformin may increase effectiveness
- Quercetin
- Reishi mushroom
- Resveratrol
- Silibinin/Silymarin/Milk Thistle
- Sulforaphane
- THC (from cannabis)
- Tocotrienols
- Turkey Tail (Coriolus Versicolor)
- Vitamin D3
COX-2 Signaling
Enzyme that promotes inflammation and angiogenesis, suppresses NK cells and TH1, and reduces apoptosis. Associated
with brain mets, lung mets and correlated with obesity and poor outcome. Chemotherapeutic agents induce COX-2 activity.
ER+HER2-: Trials have shown that COX-2 inhibitors had little effect in this subtype. However, the presence of COX-2 in tumors that
are ER+, normal for p53 and HER2- is a more important indicator of poor prognosis than other subtype, indicating that inflammation is
an important factor underlying ER+HER2- breast cancer.

TPBC: Trials have shown that COX-2 inhibitors had little effect in ER+ disease. However, the effect of COX-2 in HER2+ breast cancer
is important so blocking should be considered.

HER2-Enriched: Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation.
Blocking both pathways may improve outcomes.

TNBC: Highly expressed in TNBC. COX-2 regulates TGFβ-induced breast cancer stem cells in triple-negative breast cancer
Substance Notes
- Aspirin (or willow bark) *reduced breast cancer deaths shown for early-stage tumors not Stage 4.
- Bromelain
- CBD (from Cannabis)
- Baicalein
- Curcumin
- Danshen (Salvia Miltiorrhiza) *specifically Salvianolic acid
- EGCG
- Feverfew
- Ginger
- Grapeseed/skin extract
- Honokiol
- Melatonin
- Modified Citrus Pectin (MCP) *better in comination with Honokiol
- NSAID *celebrex or other prescription NSAID
- Olive Polyphenols *specifically oleuropein
- Omega-3 EPA/DHA
- Omega-6 GLA
- Resveratrol
- Wasabi
5-LOX Signaling
Oxidative enzymes that activate pro-inflammatory pathways like NFkB. A key player in the development of invasive breast
cancer. Associated with bone, lung, liver, and brain mets. Eating a diet high in Omega-6 linoleic acid can increase 5-LOX
and risk of breast cancer based on gene polymorphisms. Expression of 5-LOX is highly correlated with obesity.
ER+HER2-: No specific information though 5-LOX is correlated with obesity in estrogen positive cancers.
TPBC: 5-LOX is associated with brain mets. 5-LOX is correlated with obesity in estrogen positive cancers.
HER2-Enriched: 5-LOX is associated with brain mets.
TNBC: Highly expressed in TNBC and associated with bone mets. Inhibiting LOX reduces collagen cross-linking and fibronectin
assembly, increases drug penetration, apoptosis, and sensitization to chemotherapy.

Substance Notes
- Boswellia *Must contain AKBA form in addition to standardized boswellic acids.
- Feverfew
- Curcumin
- Omega-3 EPA/DHA
- Resveratrol
MAPK Signaling (Ras/MEK/ERK)
The Mitogen Activated Protein Kinases pathway (MAPK) is also known as the Ras/MEK/ERK pathway. It is a chain of
proteins within the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of
the cell. MAPK is highly stimulated by glucose and insulin.
ER+HER2-: Less common in Luminal A though found in 44% of Luminal B tumors (see Fig. 3 of ref). Plays a role in Tamoxifen
resistance. Aromatase inhibitors can upregulate MAPK, which can lead to therapy resistance.
TPBC: Somewhat common in TPBC, found in 44% of of tumors (see Fig. 3 of ref) .Plays a role in Tamoxifen resistance.
HER2-Enriched: Nearly all HER-Enriched tumors carry this mutation so it is important to block (see Fig. 3 of ref).
TNBC: One of the most important TNBC pathways to block as part of this pathway is found in about 50% of TNBC tumors (see Fig. 3
of ref). MAPK has been found to regulate the proliferation and apoptosis resistance in TNBC cells. MAPK and EGFR expression levels
were increased in TNBC patients (compared with paratumor tissues), and were associated with lymph node metastasis, advanced
clinical stage, recurrence and metastasis, and poor survival rate.
Substance Notes
- Andrographolide
- Artemisinen/Artusenate
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Baicalein
- Beta-sitosterol *in renal cell carcinoma in vitro
- Black Seed Oil (Nigella Sativa)
- Bromelain
- Curcumin
- Omega-3 DHA
- Fisetin *may cause liver toxicity if derived from wax tree
- Flaxseed *Effects due to ALA to DHA conversion, not ALA alone
- Fucoidan
- Fucoxanthin
- IV Vitamin C
- Lycopene *take with oil-based products such as Black Cumin Seed Oil or Omega-3
- Mebendazole
- Metformin *Indirectly via downregulation of ERK and Akt. Take a B12 supplement while on Metformin.
- Melatonin
- Panax Ginseng
- Quercetin
- R-Alpha Lipoic Acid (no 'S' )
- Spatholobus suberectus
- Sulforaphane
- Tocotrienols
MTAP Pathway
MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. Several research groups have
shown that MTAP acts as a tumor suppressor and that the gene is deleted in some aggressive tumors. Read more
ER+HER2- : MTAP gene is not commonly deleted in ER+HER2- tumors.
TPBC: No information available but likely not common.
HER2-Enriched: No information available but likely not common.
TNBC: One of the most important TNBC pathways to block. Dietary restriction of the amino acid methionine suppresses breast cancer
metastastasis in TNBC.
Substance Notes
- Curcumin
- Diet Low Methionine/Cysteine
PDK1 Pathway
Phosphoinositide-dependent kinase 1 (PDK1) is a proximal signaling molecule of phosphatidylinositol 3-kinase, which is
required for metabolic activation of (PI3K/AKT/mTOR signaling pathway) and is overexpressed in breast cancer. Note:
PDK1 signalling actions may be regulated via inhibition of HIF1a pathway and PI3K/AKT/mTOR signaling pathways.
ER+HER2- :
TPBC:
HER2-Enriched:
TNBC:
Substance Notes
- Aspirin (or willow bark)
- Dichloroacetate (DCA)
- Quercetin
To be added in future. *View HIF1a pathway inhibitors here and PI3K/AKT/mTOR signaling pathways here

SphK1 Pathway
 Sphingosine kinase 1 (SphK1) is one of the central enzymes in maintaining sphingosine-1-phosphate (S1P), a "pro-
survival" cell growth and survival molecule that is activated by a pro-inflammatory cytokines (immune system), transforming
growth factor β (TGF-β), tumour necrosis factor α (TNr-α), and several growth factors. SphK1 upregulates Akt and MAPK
signaling, contributing to aggressiveness of metastasic breast cancer, both estrogen-driven and non-estrogen driven.I
ER+HER2- : Highly expressed in metastastic breast cancers
TPBC: Highly expressed in metastastic breast cancers
HER2-Enriched: Highly expressed in metastastic breast cancers
TNBC: Highly expressed in TNBC
Substance Notes
- Ellagic acid *See Typical Clinical Use table for list of dietary sources
- Quercetin
*View TGF-β pathway inhibitors here
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
Navigating on a Desktop: Select which sheet (Pathway) you want to open using either the pop up menu or the permanent tabs at the
botom of the page.The Google Worksheets all sheets pop-up window menu appears when you click on the 5 small horizontal lines in
the bottom left corner of the screen, and the navigation tabs always appear at the very bottom of your screen.
Navigating on a Mobile Device: You will notice that the worksheet navigation tabs at the very bottom of your screen will hide once
you scroll down the page. Scroll up the page and the navigation tabs will re-appear. When all navigation tabs and menus vanish click
on the little 'check mark' symbol that appears at the very top left corner of the screen to move out of edit mode and back into into
navigation mode.
 Dysregulate Metabolism
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION: The cancer takes control over normal metabolic pathways to gain energy to grow. Off-label drugs, herbs, and nutritional
supplements can be used to block these pathways and starve the cancer of energy. These pathways can be blocked ("Starve") either
along with or alternating with oncology treatments like chemotherapy or radiation ("Kill") and/or integrative oncology treatments like IV
Vitamin C, IV curcumin, or other oxidative treatments. Because of interactions, some herbs and natural substances must be avoided for a
period of time around the treatment. (Consult an integrative practitioner for advice.) Read more about this here. An important point
about these energy pathways is that not all of these are important for all breast cancers at all stages. For example, when in remission,
KEY: ER+HER2- includes ER+PR+HER2- and ER+PR-HER2-, TPBC includes ER+PR+HER2+ and ER+PR-HER2+, HER2-Enriched includes ER-PR-
it is more important to encourage autophagy than to block it. All of the information given below is based on an active cancer diagnosis
HER2+ , and TNBC includes ER-PR-HER2-.
and should be modified for those who are in remission.
SPECIAL CONSIDERATIONS for ER+: Some substances may require further exploration as to their use in ER+ breast cancer (HER2+ or
HER2-). For more information, see ER+ Special Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.
—Glucose Pathways—
—Fatty Acid Pathways—
—Glutamine Pathways—
—Glucose Pathways—
Through the glucose pathways, cancer derives fuel by converting glucose from carbohydrates. Blood sugar spikes from
simple carbohydrates are most dangerous though any carbohydrate consumption can contribute glucose so a low-glycemic
fiber-rich diet is typically recommended.
ER+HER2-: Blocking glucose pathways is important for all stages; particularly important to block glucose pathways to reduce resistance
to Tamoxifen, AI, Faslodex, Piqray, or a CDK4/6 inhibitor. Blocking OXPHOS and Glycolysis is particularly important, especially when
limiting dietary glucose and/or when taking Tamoxifen/AIs/Faslodex. Inhibition of Aerobic Glycolysis Represses Akt/mTOR/HIF-1α Axis
and Restores Tamoxifen Sensitivity in Antiestrogen-Resistant Breast Cancer Cells. A protein upregulated in glycolysis appears to be
important in upregulating the estrogen receptor, pointing to the need to block glycolysis in ER+ breast cancers.
TPBC: HER2+ breast cancers depend heavily on glucose for energy, especially glycolysis and lactate. If taking Tamoxifen or AI and
Herceptin (and likely Kadcyla, Enhertu, and Tucanatib), blocking Aerobic Glycolysis appears to be particularly important to reduce
Herceptin resistance, making IV Vitamin C a particularly good choice. A protein upregulated in glycolysis appears to be important in
upregulating the estrogen receptor, pointing to the need to block glycolysis in ER+ breast cancers. Pentose Phosphate doesn't appear
to be particularly important except possibly in brain metastases. Increased Lactate production is important in HER2+.

HER2-Enriched: HER2+ breast cancers depend heavily on glucose for energy, especially glycolysis and lactate. Upregulated Aerobic
Glycolysis is correlated with Herceptin resistance (and likely Kadcyla, Enhertu, and Tucanatib resistance), making IV Vitamin C a good
choice. Pentose Phosphate doesn't appear to be particularly important except possibly in brain metastases. Increased Lactate
production is important in HER2+.
TNBC: TNBC typically have a high rate of Glycolysis and increased Lactate production.

Glucose Transporters
Substance Notes
- Beta-sitosterol
- Cinnamon (not culinary) *standardized to Cinnamaldehydes and phenolic compounds.
- Curcumin
- EGCG
- Fucoidan
- Kaempferol
- Quercetin
- Reishi Mushroom
- Resveratrol
- Silibinin/Silymarin/Milk Thistle
- Statin *lipophilic statin

Insulin
Substance Notes
- Berberine
- Chromium
- Diet Low GI
- Exercise
 - Garlic extract *Fresh raw garlic is preferable; efffects come from hydrogen sulfide
- Metformin *Ensure you take a B12 supplement while on Metformin as it depletes B12

Pentose Phosphate
Substance Notes
- d-Mannose
- DHEA not for ER+
- EGCG *partial inhibition
- Polydatin
- Silibinin/Silymarin/Milk Thistle

OXPHOS
When blocking glycolysis, OXPHOS is upregulated so it should be blocked as well. In addition, Upregulated OXPHOS also
allows dormant breast cancer cells to stay alive but quiescent for long periods of time, thus making this an important pathway
to block during remission, especially in ER+HER2- where late (5-20 year) recurrence is more common.
Substance Notes
- Berberine
- Citrus Bergamot
- Doxycycline
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- Niclosamide

Aerobic Glycolysis

Aerobic glycolysis refers to the "Warburg Effect," in which tumors switch to a method of energy production that requires very
little oxygen, which is opposite from normal cells that use oxidative phosphorylation to produce energy. This process is driven
by HIF-1 and mutated TP53, so refer to HIF-1 and TP53 in Invade/Metastasize to downregulate aerobic glycolysis. Mutated
oncogenes RAS and MYC are also associated with the tumor's dependence on glycolysis. Upregulated glycolysis also allows
dormant breast cancer cells to stay alive but quiescent for long periods of time, thus making this an important pathway to
block during remission, especially in ER+HER2- where late (5-20 year) recurrence is more common.
Substance Notes
- 2 Deoxyglucose
- 3-Bromopyruvate
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Aspirin (or willow bark)
- Auranofin
- Betulinic acid *in Chaga mushroom - extract available from MCS formulas
Baicalein
- Chrysin
- Cinnamon (not culinary) *standardized to Cinnamaldehydes and phenolic compounds.
- Citrate
- d-Mannose
- Dichloroacetate (DCA)
- EGCG
- Fermented Wheat Germ Extract
- Honokiol
- Hydroxycitrate (Garcinia Cambogia)
- Intermittent Fasting
- IV Vitamin C
- Ketogenic Diet
- Melatonin
- Metformin *May be more powerful when combined with propranalol
- Modified Citrus Pectin (MCP)
- N-acetyl cysteine (NAC)
- Olive Polyphenols *specifically oleanolic acid)
- Propranolol
- R-Alpha Lipoic Acid (no 'S' ) *IV alpha-lipoic acid is superior to the oral form
- Reishi mushroom *specifically oleanolic acid)
 - Silibinin/Silymarin/Milk Thistle
- Sulforaphane
Syrosingopine *best combined with Metformin
- Tocotrienols
- Vitamin D3
*Other than IVC,2-DG, and 3-BP, these may only be partially blocking pathway so use multiple

LACTATE
Tumors produce lactate from glucose, in a process known as the "Warburg Effect." Read more here. And here.
Substance Notes
- Fermented Wheat germ extract
- Hari Taki [1] *shown in glioblastoma
- Luteolin
- NSAID *specifically diclofenac, shown in melanoma
- Quercetin
- Reishi Mushroom
- Silibinin/Silymarin/Milk Thistle
- Spatholobus suberectus
Syrosingopine *best combined with Metformin
Hexokinase II (HKII) Bound to VDAC (Activate VDAC)
Part of the energy reprogramming by cancer cells is the translocation of HKII so that it binds to the Voltage-dependent anion-
selective channel (VDAC) and blocks its function, providing ATP for glycolysis and preventing apoptosis. VDACs transport
ATP and other small ions and metabolites across the outer mitochondrial membrane; various VDACs with different functions
have been identified and named VDAC 1, 2, AND 3. Elevated expession of PI3K/Akt/mTOR drives this process. Elevated HK
II Expression Confers Acquired Resistance to Tamoxifen
Substance Notes
- Aspirin (or willow bark)
- CBD (from Cannabis)
- Baicalein
- Black Seed Oil (Nigella Sativa)
- Curcumin
- Fenofibrate
- Itraconazole *Caution, strong CYP3A4 inhibitor and may up-regulate autophagy
- Licorice root
- Metformin
- Quercetin
- Solomons Seal Whole herb minus seeds which are toxic

—Fatty Acid Pathways—

Fatty acid pathways are methods by which the cancer creates fuel from fat— either from breakdown of cholesterol (FAO,
SREBP-2, Mevalonate) or indirectly from glucose or glutamine (SREBP-1, ACLY, FAS), Fatty acid pathways are also blocked
by way of blocking Hypoxia Inducible Factor-1 (HIF-1) under Invade/Metastasize. If taking Metformin, it may be important to
block Fatty Acid Oxidation (FAO), either directly or indirectly, though this has only been demonstrated in one in vitro study;
population studies connect Metformin use in diabetics with lower risk of breast cancer recurrence. Fatty acid pathways are
particularly upregulated in early-stage breast cncer that doesn't respond completely to chemotherapy as well as metastastic
breast cancer. Stage 4 breast cancers can revert to using FAO, and other fatty acid pathways, creating resistance to
chemotherapy.

ER+HER2-: High saturated fat diets are correlated with greater risk of ER+ breast cancer. FAS is upregulated in ER+ breast cancer. If
taking Tamoxifen, blocking FAS is important to reduce resistance. If taking Tamoxifen, AIs, or Faslodex, blocking the SREBP-2 and
Mevalonate pathways is particularly important to reduce resistance. Resistance to estrogen blocking therapies in lobular type is
particularly driven by fatty acid pathways.
TPBC: HER2+ breast cancers are particularly driven by fatty acid pathways, especially SREBP-1, ACLY, FAS, SREBP-2, and
Mevalonate. TPBC is also driven by FAS and involving estrogen receptor signaling. HER2+ breast cancer uses SREBP-1/FAS and
SREBP-2/Mevalonate to develop resistance to targeted therapies like Herceptin, Enhertu,Tykerb and Tucanatib. If taking Tamoxifen,
AIs, or Faslodex, blocking the FAS, SREBP-2 and Mevalonate pathways is particularly important to reduce resistance.
HER2-Enriched: HER2+ breast cancers are particularly driven by fatty acid pathways, especially SREBP-1, ACLY, FAS, FAO, SREBP-
2, and Mevalonate. HER2+ breast cancer uses SREBP-1/FAS and SREBP-2/Mevalonate to develop resistance to targeted therapies
like Herceptin, Enhertu,Tykerb and Tucanatib. Conversely, however, palmitic acid (found in meat, butter, sunflower oil) appears to be
cytotoxic to HER2-Enriched cell lines and increases AMPK.
TNBC: TNBC tumors have a high level of FAO but don't typically use FAS.

SREBP-1
Feeds into FAS and is driven by Aerobic Glycolysis (Glucose Pathway), so Aerobic Glycolysis blockers also apply
Substance Notes
- Andrographolide
- Berberine
- Reishi Mushroom
ACLY (ATP Citrate Lyase)
Substance Notes
- Hydroxycitrate (Garcinia Cambogia)
Fatty Acid Synthesis (FAS)
SREPB-1 upregulates FAS so refer to those pathway blockers as well
Substance Notes
Berberine + Aspirin
- EGCG *Weaker than luteolin and quercetin
- Luteolin
Metformin + Aspirin
- Omeprazole *Use short term only. Clinical trial showed improved response of chemo drugs in TNBC.
- Quercetin
- Sea buckthorn oil
- Sulforaphane
ACC (Acetyl-CoA Carboxylase)
ACC is a key enzyme involved in FAS.
Substance Notes
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
more to be added.

FAO

FAO is upregulated in chemotherapy and targeted treatments of metastatic breast cancer, leading to increased reactive
oxygen species (ROS), which drive further cancer progression. Brain metastases may be particularly driven by FAO. Based
on one cell line study, it may be important to block FAO (see Generate Energy) directly or indirectly* if strongly upregulating
AMPK with Metformin when on estrogen blocking therapy. Effect not established in vivo, though a recent clinical trial
showed no improvement in recurrence risk for women using Metformin as an adjuvant therapy in remission, except
for a subset with HER2+ breast cancer.

HIFs also drive FAO, so refer to the list of HIF pathway blockers under the Invade/Metastasize tab
Substance Notes
- Doxycycline
- Mildronate
- Omega-3 DHA *Best combined with delta-tocotrienol to block lipid droplet formation
*Based on personal communication with Jane McLelland, a combination of Statin + Berberine or combinations of natural substances such as
Andrographolide + Citrus Bergamot/RYR +Omega-3 DHA or Citrus Bergamot/RYR + Berberine + Omega-3 DHA may indirectly block FAO. https:
//www.cambridge.org/core/journals/british-journal-of-nutrition/article/effect-of-linolenic-acid-and-dha-intake-on-lipogenesis-and-gene-expression-
involved-in-fatty-acid-metabolism-in-growingfinishing-pigs/60881A0D144CE7334D1288433626C712
Mevalonate
Lipophilic statin drugs, citrus bergamot + berberine, red yeast rice (with verified Monakolin K content), lycopene and
andrographolide are the only options shown to block mevalonate. Niacin, amla, and omega-3 EPA/DHA reduce cholesterol
through other mechanisms but shouldn't be relied upon to block the mevalonate ptahway. Note that antioxidants like
lycopene should not be used during a kill phase and that most EPA/DHA supplements contain alpha-tocopherol, an
antioxidant.
Substance Notes
- Andrographolide
- Citrus Bergamot DO NOT TAKE WITH TAMOXIFEN *Best combined with berberine
- Lycopene
- Red Yeast Rice *Use a brand with verified Monakolin K content 6-10 mg per day
 - Statin *lipophilic statin
SREBP-2
Optimally take two from list: herbs and omega-3 EPA/DHA likely to reduce, not block.
Substance Notes
- Andrographolide
Dandelion Also blocks FADS2, which is downstream
- Dipyridamole
- Luteolin
- Omega-3 EPA/DHA
- Statin *lipophilic statin
- Tocotrienols

—Glutamine Pathways—
This section includes pathways through which cancer drives fuel from glutamine and other amino acids.Glutamine is an
amino acid that comes from the breakdown of protein, which can come from excess in the diet or from the breakdown of
cancer cell debris and normal tissue. Use of glutamine as a fuel source is dependent on breast cancer subtype and stage.
It's not actually the glutamine itself that provides the fuel for cancer but the conversion of glutamine to glutamate via a process
called glutaminolysis. Also important is input from other amino acids such as methionine, aparagine, aspartamine, arginine,
and cysteine. Although dietary measures can reduce glutamine and other amino acids, is most important to block the enzyme
glutaminase because it is impossible to eliminate glutamine completely from the diet. Glutamine metabolism in tumors is a
complex topic, with much research still to be done.
ER+HER2-: IGF-1 is the most important glutamine pathway for ER+HER2- at all stages. As cancers progress to Stage IV and
particularly during chemotherapy and radiation therapy, blocking Nucleoside Salvage becomes important.
TPBC: Glutamine pathways particularly important in HER2+ are Glutaminolysis, mTOR, and Macropincytosis. In addition, IGF-1 is
associated with greater risk of TPBC breast cancer in patients with high BMI and should be blocked in TPBC. IGF-1 is associated with
resistance to Herceptin and related therapies. However, high IGF-1 levels are associated with higher recurrence risk ONLY in HER2+
patients with high BMI. High circulating IGF-1 was actually associated with lower recurrence risk in women with normal BMI. During
chemo and radiation therapy it is important to block cancer autophagy (Macropincytosis and Nucleoside Salvage). Use of chloroquine
with monoclonal antibody drugs like Herceptin and its newer relatives may be contraindicated as a well-functioning immune system is
required for anti-HER2 therapies. High Glycine levels have been found in HER2+ tumors but it's unknown if dietary glycine has an impact
or if the cancer causes de novo synthesis..
HER2-Enriched: Glutamine pathways particularly important in HER2+ are Glutaminolysis, mTOR, and Macropincytosis. IGF-1 is
associated with resistance to Herceptin and related therapies. However, high IGF-1 levels are associated with higher recurrence risk
ONLY in HER2+ patients with high BMI. High circulating IGF-1 was actually associated with lower recurrence risk in women with normal
BMI. During chemo and radiation therapy it is important to block cancer autophagy ( Glutaminolysis, mTOR, and Macropincytosis).
Use of chloroquine with monoclonal antiobody drugs like Herceptin and its newer relatives may be contraindicated as a well-functioning
immune system is required for anti-HER2 therapies. High Glycine levels have been found in HER2+ tumors but it's unknown if dietary
glycine has an impact or if the cancer causes de novo synthesis.
TNBC: TNBC tumors show increased Glutaminolysis compared with ER+ tumors. Serine, Proteosome,and PIN1 are important
metabolic pathways for TNBC though drug inhibition of proteosome in remission may not be advised.

IGF-1
Insulin-like Growth Factor-1 (IGF-1) is a nutrient-responsive growth factor that activates MAPK and PI3K/AKT signaling which are a
critical drivers of tumor growth. Preclinical evidence shows that IGF-1 and IGF-1R are the main factors associated with breast cancer
bone metastasis. When taking aromatase inhibitors at any stage, it is important to block this pathway to reduce resistance.
Substance Notes
- Citrate
- Diet No Sugar, No Dairy
- Longer fasts
- Metformin
- R-Alpha Lipoic Acid (no 'S' )
- Sodium Selenite
- Tamoxifen
- Vitamin D3
Glutamine OXPHOS
Substance Notes
- Berberine
- Doxycycline Don't take on an empty stomach
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- Niclosamide
 mTOR
Substance Notes
- Berberine
- Burdock (Arctigenin)
- Danshen (Salvia Miltiorrhiza)
- Honokiol
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- Olive Polyphenols
- Omega-3 EPA/DHA
- Rapamycin
- Reishi mushroom
Cancer Autophagy-Macropincytosis
Substance Notes
- Black Seed Oil (Nigella Sativa)
- Desloratidine
- Hydroxychloroquine/Chloroquine *May not be advised with some targeted therapies; consult oncology pharmacist
- Loratadine (Claritin)
- Metformin *New study in breast cancer cell lines
- Propranolol
Cancer Autophagy - Nucleotides & Nucleosides
Substance Notes
- Dipyridamole
- Leflunomide
- Silibinin/Silymarin/Milk Thistle *blocks pyrimidine synthesis in TNBC cell line
- Sulforaphane *shown in ER+HER2- cell line, limited evidence only for ER+
Glutaminolysis
Substance Notes
- BPTES
- Caffeic Acid
Curcumin + Ursolic Acid
- EGCG
- Hesperetin
- Metformin *New study in breast cancer cell lines
Resveratrol + Ursolic Acid
Serine (Glycine)
Substance Notes
- Aspirin (or willow bark)
Proteasome
High levels of proteosomes allow the cancer cell to avoid apoptosis needed to degrade damaged proteins
Substance Notes
- Apigenin
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Curcumin
- Disulfiram
- EGCG
- Genistein
- Quercetin
PIN1
PIN1 is an enzyme that alters the structure of serine/threonine/proline amino acid complex and is activated in aggressive
breast cancers)
Substance Notes
- EGCG
- Juglone (Black Walnut)
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
 Invade/Metastasize
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION: This category combines three individual Hallmarks of Cancer as described by Hanahan (2011)–Evade Growth Suppression
Signals, Create Blood Supply (Angiogenesis), and Develop Metastases. Additional details will be added in future.
KEY: ER+HER2- includes ER+PR+HER2- and ER+PR-HER2-, TPBC includes ER+PR+HER2+ and ER+PR-HER2+, HER2-Enriched includes ER-
PR-HER2+ , and TNBC includes ER-PR-HER2-.
SPECIAL CONSIDERATIONS for ER+: Some substances may require further exploration as to their use in ER+ breast cancer (HER2+ or
HER2-). For more information, see ER+ Special Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.
—Growth Suppression/DNA Repair—
—Angiogenesis—
—Develop Metastases—
—Growth Suppression/DNARepair
Normal cells have genes that code for suppressing growth and repair of damaged cells but cancer cells carry mutations in
these genes.

TP53 Gene
This tumor suppressor "TP53" gene is frequently mutated in breast tumors. Also, many people with breast cancer also have
acquired mutations or "SNPs" in TP53 in their genome found through testing such as Nutrition Genome. A mutated TP53
can't signal for repair or cell death to respond to cell damage (caused by VOCs from grilled food, pesticides, etc.). Loss of
p53 function allows tumor cells to upregulate glycolysis.

ER+HER2-: Improving p53 function is important to maintaining sensitivity to aromatase inhibitors and possibly to CDK4/6 inhibitors.

TPBC: Improving p53 function is important to maintaining sensitivity to aromatase inhibitors.

HER2-Enriched: Very important to improve p53 function in HER2-Enriched as it is mutated in 78% of tumors (see Fig. 3 of ref).
TNBC: Very important to improve p53 function in TNBC as it is mutated in 91% of tumors (see Fig. 3 of ref). There is also a relationship
between TP53 and BRCA mutations.

Substance Notes
- Anthocyanins *red & blue fruits/veg
- Ashwagandha
- Astragalus
- Curcumin
- EGCG
- Honokiol
- IP-6 *take away from all other supplements
- IV Vitamin C
- Melatonin *higher dose more effective per Doris Loh
- Narigenin
- Olive Polyphenols *Specifically oleuropein
- PEITC
- Resveratrol
- Selenium
- Sulforaphane
- Tocotrienols
- Vitamin D3 *caution with high level of vitamin D if your tumor (not you) has mutated p53.
- Zinc

TP21 Gene
This tumor suppressor "TP21" gene is frequently mutated in TNBC breast tumors and is another tumor suppressor like TP53.

ER+HER2-: NA
TPBC: NA
HER2-Enriched: NA
TNBC: Very important to improve p21 function in TNBC There is also a relationship between TP21 and BRCA mutations.

- Ashwagandha *best combined with sulforaphane

- Sulforaphane *best combined with ashwagandha
PARP-1
PARP-1 is an enzyme that helps with the recruitment of DNA repair enzymes that execute DNA repair. It is particularly
important for BRCA 1/2 mutation carriers. Inhibiting PARP-1 during chemotherapy or radiotherapy for BRCA 1/2 tumors
exposes an Achilles heal and causes increased cell death. PARP inhibitors can also be used in BRCA 1/2 cancers in
remission to inhibit the repair of damaged DNA, which is common with BRCA mutations. PARP inhibitors as adjuvant therapy
for BRCA 1/2 breast cancers are being tested in clinical trials.
ER+HER2-: Important for BRCA 1/2
TPBC: Importance unknown.
HER2-Enriched: Importance unknown.
TNBC: Important for BRCA 1/2
Substance Notes
- Fermented Wheat Germ Extract
- Fisetin *may cause liver toxicity if derived from wax tree
- Panax Ginseng

Keap1/Nrf-2/ARE (up-regulate)–AVOID WITH OXIDATIVE TREATMENTS

Signals genes for antioxidants inside the cell that repair DNA damage from free radicals and is needed for normal cell
function but can be up-regulated in more aggressive breast cancers and in BRCA-1 mutations. Upregulating nrf-2 down-
regulates NFkB, which helps control breast cancer. However, blocking nrf-2 may be desirable in active cancer during certain
chemotherapy and other oxidative therapies like IV vitamin C, HBOT, and ozone because nrf-2 is part of the glutathione
system.*

Substance Notes
- Andrographolide
- Baicalein
- Boswellia *Must contain AKBA form in addition to standardized boswellic acids.
- Carnisol
- Curcumin
- EGCG
- Garlic extract
- Gingko Biloba (Gingketin)
- Grapeseed/skin extract
- MSM
- Olive Polyphenols *Specifically hydroxytyrosol
- Silibinin/Silymarin/Milk Thistle
- Sulforaphane
*THIS IS A COMPLEX TOPIC. Consult experienced integrative practitioner before using the above substances during the
active phase of chemotherapy or radiation therapy, in late-stage breast cancers, or in active BRCA-1 breast cancers, as
Nrf-2 up-regulation may be contra-indicated in these cases. Note that these substances have other POSITIVE EFFECTS
in these situations as they inhibit other pathways that may be more important to a protocol.
Keap1/Nrf-2/ARE (inhibit)
Inhibiting Nrf-2 may be desirable in some situations during chemotherapy or radiation therapy. **

Substance Notes
- Apigenin
- Chrysin
- Fenugreek (Trigonelline)
- Luteolin
**Consult an experienced integrative practitioner. Certain drugs like dexamethasone and Retin-A also inhibit Nrf-2.
Rb
 A necessary protein that prevents excessive cell growth and is often inactivated in breast cancer because of mutations in a
gene called cyclin D1. Rb mutations may be responsible for developed resistance to CDK4/6 inhibitor drugs.
Substance Notes
- Honokiol *only shown in lung cancer
More to be added in future. Let us know if you learn anything.
TGF-b
Linked with tumor progression, cell motility, cancer invasiveness, and metastasis to bone (RANKL) and lungs. TGF-b
overexpression is a key factor in breast cancer's ability to suppress the immune system. TGF-b faciltates the ability of
circulating tumor cells to associate with platelets, which protects CTCs from natural killer cells and increases the cancer's
ability to metastasize. In normal cells,TGF-b is actually known for its anti-proliferative effects, yet cancer cells redirect its
activities away from suppressing to activating cell proliferation via Epithelial to Mesenchymal transition (EMT), which is
important in cancer stem cells conversion to cancer cells. TGF-b is particularly important in cancer stem cells' progression to
brain metastases. TGF-b is very important to block during treatment especially for late-stage breast cancers, but its
importance during remission is unclear.
ER+HER2-: TGF-b is implicated in resistance to tamoxifen and aromatase inhibitors.

TPBC: Even in early-stage HER2+, TGF-b should be blocked because crosstalk with the overexpressed HER2/neu receptor converts
TGF-β from a tumor suppressor to a malignancy-promoting factor. Enhanced TGF-b signaling leads to non-coding RNA that is correlated
with resistance to Herceptin and its analog drugs.

HER2-Enriched: Even in early-stage HER2+, TGF-b should be blocked because crosstalk with the overexpressed HER2/neu receptor
converts TGF-β from a tumor suppressor to a malignancy-promoting factor. Enhanced TGF-b signaling leads to non-coding RNA that is
correlated with resistance to Herceptin and its analog drugs.
TNBC: TGF-b contributes to disease progression by increasing Androgen Receptor expression in TNBC.

Substance Notes
- Artemisinen/Artusenate
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Baicalein
- Berberine
- Bromelain
- Curcumin
- Dipyridamole
- EGCG
- Ellagic acid
- Follistatin
- Fucoidan
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- Olive Polyphenols
- Quercetin
- Panax Ginseng
- R-Alpha Lipoic Acid (no 'S' )
- Reishi Mushroom
- Resveratrol
- Silibinin/Silymarin/Milk Thistle
- Ursolic Acid

HSP90
A protein that enables the activation of many signaling protein kinases that are needed for cancer cell growth and
proliferation. These include ErbB2/HER2, EGFR, Src, Akt, and Ras (MAPK, MEK). HSP90 has been particularly implicated in
breast cancer stem cells and brain metastases. No oncology drugs are currently available though some are in clinical trials for
other cancer types.
ER+HER2-: to be added
TPBC: HSP90 is implicated in Herceptin resistance and likely resistance to all HER2-targeted therapies.
HER2-Enriched: HSP90 is implicated in Herceptin resistance and likely resistance to all HER-targeted therapies.
TNBC: to be added

Substance Notes
- EGCG
- Melatonin *Specifically studied in HER2+ with Neratinib, approximately 240 mg per day human equiv.
 - Spatholobus suberectus
IGF-1
Insulin-like Growth Factor-1 (IGF-1) is a nutrient-responsive growth factor that activates MAPK and PI3K/AKT signaling which are a
critical drivers of tumor growth. Preclinical evidence shows that IGF-1 and IGF-1R are the main factors associated with breast cancer
bone metastasis.
Substance Notes
Please refer to Dysregulate Metabolism tab/Glutamine pathway

—Angiogenesis—
Tumors create numerous blood vessels in a process called angiogenesis to bring nutrients and oxygen. But tumors are
starved for oxygen because these vessels are chaotic and leaky so they compensate by creating ways to thrive in a low-
oxygen, low-glucose environment. The tumor's ability to create HIFs and VEGF is an important characteristic of the Tumor
Microenvironment, summarized here.

HIFs (Hypoxia-Inducible Factors)

HIFs promote hypoxia (low oxygen) in cells via Heat shock Proteins (HSPs), which causes them to create new blood vessels
(VEGF), upregulate glucose transporters, aerobic glycolysis, and fatty acid storage, create cancer associated fibroblasts
(CAFs), and resist death. HIFs are upregulated by the PI3K/Akt/mTOR pathway, so those inhibitors also inhibit HIFs. Anemia
resulting from chemotherapy drives hypoxia and HIFs, making this an important pathway to block during chemotherapy
treatments.
ER+HER2-: Tamoxifen upregulates HIF-alpha, which can create resistance and lead to upegulation of the Wnt-/b-catenin pathway.
Taking these substances may reduce the potential for Tamoxifen and AI resistance. HIF-alpha-1 reduction makes CDK4/6 inhibitors
work better (palbociclib, ribociclib, and abemaciclib).
TPBC: HER2/neu upregulates HIF-1 through the PI3K/Akt/mTOR pathway. Tamoxifen upregulates HIF-alpha, which can create
resistance and lead to upregulation of the Wnt-/b-catenin pathway. Taking these substances may reduce the potential for Tamoxifen
resistance.
HER2-Enriched: HER2/neu upregulates HIF-1 through the the PI3K/Akt/mTOR pathway.
TNBC: HIF-1 is highly expressed in TNBC and can be increased during chemotherapy, driving the growth of resistant breast cancer
stem cells.
Additional Interventions for reducing HIF-1 from Neil McKinney, ND: (1) Correct sodium to potassium ratio, limit salt intake
and increase potassium rich vegetable and fruit intake. (2) Alkaline diet reduce salt, sugar and meat intake. (3) Aerobic
exercise at least twice a week. (4) Sodium bicarbonate up to 1/2 tsp twice daily (away from meals). (5) Hyperbaric oxygen

Substance Notes
- Amla *ovarian cancer model
- Andrographolide
- Apigenin
- Baicalein
- Betulinic acid *in Chaga mushroom - extract available from MCS formulas
- Black Seed Oil (Nigella Sativa)
- Cinnamon (not culinary)
- Danshen (Salvia Miltiorrhiza) *specifically Tanshinione II
- Fucoidan
- Garlic extract *specifically diallyl trisulfide (DATS)
- Honokiol
- Melatonin *high dose, see notes
- MSM
- Olive Polyphenols *specifically hydroxytyrosol
- Pawpaw
- Silibinin/Silymarin/Milk Thistle
- Spatholobus suberectus
- Sulforaphane
VEGF
Signaling protein that promotes growth of new blood vessels. Upregulated in majority of breast cancers; associated with
brain, lung, and liver mets.
ER+HER2-: Inhibiting VEGF expression is important for maintaining sensitivity to Tamoxifen and aromatase inhibitors.
TPBC: Inhibiting VEGF expression is important for maintaining sensitivity to Tamoxifen and aromatase inhibitors.
HER2-Enriched: VEGF is highly expressed in HER2-Enriched compared with ER+ subtypes.
TNBC: VEGF is more highly expressed in TNBC than other subtypes.

Substance Notes
- Andrographolide
- Artemisinen/Artusenate
- Apigenin
- Aspirin (or willow bark)
- Baicalein
- Beta-sitosterol *in vitro in renal cell carcinoma
- Betulinic acid *in Chaga mushroom - extract available from MCS formulas
- Black Seed Oil (Nigella Sativa) *best combined with melatonin
- Boswellia *Must contain AKBA form in addition to standardized boswellic acids.
- Chrysin *aromatase Inhibitor; suppressed lung mets in a mouse model
- Cinnamon (not culinary)
- C-Statin
- Curcumin *best combined with EGCG
- Danshen (Salvia Miltiorrhiza) *specifically Salvianolic acid and Tanshinione II
- EGCG *best combined with Curcumin
- Ellagic acid
- Flubendazole
- Fucoidan
- Fucoxanthin
- Gingko Biloba (Gingketin) *Specifically gingkolide B
- Grapeseed/skin extract
- Kaempferol
- Luteolin
- Modified Citrus Pectin (MCP)
- Mebendazole
- Melatonin
- Omega-3 EPA/DHA *human clinical trial
- Pawpaw
- Silibinin/Silymarin/Milk Thistle
- Sulforaphane
- Mistletoe
- MSM
- Myricetin
- Panax Ginseng
- Propranolol
- Reishi Mushroom
- Resveratrol
- Tamoxifen
- Tocotrienols
- Vitamin D3
Fibroblast Growth Factor Receptor (FGF-R)
Along with VEGF, FGF binds to cell surface-expressed receptors equipped with tyrosine kinase activity, signalling pathways
that regulate proliferation, migration and differentiation of endothelial cells. FGF activates three major signaling pathways:
MAPK, PI3K/Akt, and STAT. Associated with progesterone receptor negativity, bone mets, brain mets, and overall poorer
prognosis. More commonly expressed in ER+ breast cancers, both HER2- and HER2+. FGFR inhibitor drugs are in
development for use in breast cancer. Leptin is a stimulator of cancer-associated fibroblasts and is elevated in overweight
women, who are more at risk for pimary breast cancer and breast cancer metastasis.

ER+HER2-: More commonly expressed in ER+HER2-. FGFR mutations may contribute to resistance to anti-estrogen therapies. When
taking aromatase inhibitors at any stage, it is important to block this pathway to reduce resistance.
TPBC: Expressed in TPBC. Brain mets in this subtype commonly express mutations in FGFR, TP53, and FTL1. FGFR mutations may
contribute to resistance to HER2 targeted therapies as well as resistance to anti-estrogen therapies. When taking aromatase inhibitors at
any stage, it is important to block this pathway to reduce resistance.

HER2-Enriched: Expressed in HER2-Enriched. Brain mets in this subtype commonly express mutations in FGFR, TP53, and FTL1.
FGFR mutations may contribute to resistance to HER2 targeted therapies.
TNBC: Not commonly expressed in TNBC.

Substance Notes
- Baicalein
- Bromelain
- Fucoxanthin
- Modified Citrus Pectin (MCP)
- Reishi Mushroom

Platelet Activating Factor Receptor (PAF-R)

PAF is secreted in the cancer microenvironment as an inflammatory response to take over the normal activities of platelets,
neutrophils, basophils, and macrophages. PAF is increased by conventional chemotherapy and radiotherapy so it's important
to inhibit it while in treatment. PAF contributes to both metastasis and angiogenesis, the formation of blood vessels to feed
the tumor. Higher expression of PAF leads to more aggressive disease and upregulates glycolysis and fatty acid pathways.
Certain fats consumed in a Mediterranean diet such as fish oil, (omega-3 fats), sphingomyelin and phosphatidylethanolamine
(fermented dairy fat like yogurt and cheese), and phosphatidylcholine (eggs) appear to reduce PAF.
ER+HER2-: Expressed in ER+HER2- Studies suggest that hormone-therapies induce heightened sensitivity to thrombin by upregulating
PAR receptors, further increasing thromboembolic risk. Results indicate an increase in thrombin generation in breast cancer cells treated
with Tamoxifen.
TPBC: Expressed in TPBC.

HER2-Enriched: Expressed in HER2-Enriched.

TNBC: Expressed in TNBC

Substance Notes
- Bromelain
- Danshen (Salvia Miltiorrhiza)
- EGCG
- Gingko Biloba (Gingketin) *Specifically gingkolide B

- Omega-3 EPA/DHA
- Phosphatidylcholine
- Phosphatidylethanolamine (PEA)
- Sphingomyelin

Platelet Derived Growth Factor Receptor (PDGF-R)

Overstimulation of PDGF changes the cells surrounding the tumor (the stroma) so it can invade and create new blood
vessels. PDGF faciltates the ability of circulating tumor cells to associate with platelets, which protects CTCs from natural
killer cells and increases the cancer's ability to metastasize. PDGF over-expression is more common in ER-, PR-, HER2+,
and TNBC subtypes, and high expression correlates with brain metastases.

TPBC: Expressed in TPBC.

HER2-Enriched: Expressed in HER2-Enriched.

TNBC: More common in TNBC than in other types.

Substance Notes
- Danshen (Salvia Miltiorrhiza)
- Dipyridamole
- Reishi Mushroom

—Develop Metastases—
 Matrix Metalloproteinases (MMPs) are proteins found in cancer cell membranes and surrounding cells that degrade cell the
extracellular matrix to enhance invasion and metastasis. Tumor-associated macrophages (immune cells gone rogue) at the
tumor borders can supply MMPs to enhance the tumor's ability to invade tissues. Read more here about the relative
expression of MMPs and TIMPs by subtype. MMPs also act directly on tumor cells and cause them to release factors that
promote growth or suppress apoptosis. MMP-2 and -9 are particularly associated with risk of metastasis and poor prognosis,
so very important to block. MMPs are found both within the tumor and in the tissue surrounding the tumor (stroma).
Important growth factors contributing to metastasis are FGF, PDGF, and FGF, which also play an important role in the Tumor
Microenvironment, summarized here. Platelets play an important role in metastasis. Loss of E-cadherin expression, which
helps normal cells maintain their organization within the tissue, is important in most breast cancers, while inflammatory breast
cancer is characterized by an overexpression of E-cadherin.

MMP-1
Important for bone mets, lung mets and brain mets and multi-drug resistance but not very common in breast cancer.
ER+HER2-: Only found in about 10% of ER+HER2- tumors but found in 3/4 of tumor stroma samples.
TPBC: Only found in about 12% of HER2+ tumors but found in 3/4 of tumor stroma samples.

HER2-Enriched: Only found in about 12% of HER2+ tumors but found in 3/4 of tumor stroma samples.
TNBC: Only found in about 10% of TNBC tumors but found in 3/4 of tumor stroma samples.

Substance Notes
- Amla
- Curcumin
- EGCG
- Modified Citrus Pectin (MCP)
- Passiflora foetida
- Quercetin
MMP-2
Important for lung mets; may be associated with brain mets; upregulated by NF-kB. MMP-2 expression is associated with
higher risk of metastasis and poor prognosis.

ER+HER2-: Expressed in about 40% of ER+HER2- tumors.

TPBC: Found in about 40% of HER2+ tumors.

HER2-Enriched: Found in about 40% of HER2+ tumors.

TNBC: Found in about 35% of TNBC tumors.

Substance Notes
- Andrographolide
- Betulinic acid *in Chaga mushroom - extract available from MCS formulas
- Chitin
- Danshen (Salvia Miltiorrhiza)
- Diet Low Methionine/Cysteine
- Doxycycline
- EGCG
- Fucoidan
- Fucoxanthin
- Luteolin
- Mebendazole
- Melatonin
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- Myricetin
- Omega-3 EPA/DHA
- Propranolol
- Selenium
- Tocotrienols
 MMP-7
Degrades cellular structures in tissues surrounding tumors, though the role in breast cancer is not well known. MMP7
upregulation appears to happen because of loss of PTEN gene expression, especially in TNBC. Higher MMP7 expression is
associated with bone metastases. Lower expression in less invasive and slower growing tumors. NOTE: Refer to the
PI3K/akt/mTOR pathway, which is associated with loss of PTEN, for additional substances to block MMP7.

ER+HER2-: Found in about 80% of ER+HER2- tumors.

TPBC: Found in about 70% of HER2+ tumors.

HER2-Enriched: Found in about 70% of HER2+ tumors.

TNBC: Found in nearly all TNBC tumors. High expression is related to loss of PTEN.

Substance Notes
- Andrographolide
- Baicalein
- EGCG
- Poria Cocos *Especially with astragalus
MMP-9
Associated with bone and brain mets and poorer prognosis. Causes a leaky blood brain barrier and contributes to
neurodegeneration.

ER+HER2-: Not as common in ER+HER2- as in others.

TPBC: Highly expressed in HER2+, about 70% of tumors

HER2-Enriched: Highly expressed in HER2+, about 70% of tumors

TNBC: Moderate expression in TNBC, about 35% of tumors

Substance Notes
- Apigenin
- Astragalus
- Andrographolide
- Artemisinen/Artusenate
- Betulinic acid *in Chaga mushroom - extract available from MCS formulas
- Burdock (Arctigenin)
- Curcumin
- Danshen (Salvia Miltiorrhiza)
- Diet Low Methionine/Cysteine
- Dipyridamole
- Doxycycline
- EGCG
- Fucoidan
- Fucoxanthin
- Luteolin
- Modified Citrus Pectin (MCP)
- Melatonin *Important for improving blood brain barrier function.
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- Myricetin
- Omega-3 EPA/DHA *Important for improving blood brain barrier function. **2-6 g per day
- Propranolol
- Quercetin
- Reishi Mushroom
- Resveratrol
- Silibinin/Silymarin/Milk Thistle
- Tocotrienols
- Turkey Tail (Coriolus Versicolor)
- Vitamin D3
MMP-11
 Found in nearly all tumors in all subtypes. May not be significant predictor of tumor progression or prognosis.

MMP-13
Needed for building the collagen matrix for bone mineralization but overexpressed in cancer. May play a key role in bone
mets by activating MMP-9 and other enzymes.

ER+HER2-: Expressed in about 36% of ER+HER2- tumors

TPBC: Highly expressed in HER2+, about 70% of tumors

HER2-Enriched: Highly expressed in HER2+, about 70% of tumors

TNBC: Found in about 50% of TNBC tumors

Substance Notes
- Curcumin
- Rosmarinic acid
MMP-14, -15, -16
Strong predictor of tumor aggressiveness and survival time, which are called Membrane-Type Metalloproteinases (MT-
MMPs). Bind to other MMPs and activate DDRI, which creates a collagen matrix around cancer cells that keeps immune cells
from entering.

ER+HER2-: Expressed in about 54% of ER+HER2- tumors

TPBC: Highly expressed in HER2+, about 70% of tumors

HER2-Enriched: Highly expressed in HER2+, about 70% of tumors

TNBC: Found in about 70% of TNBC tumors

Substance Notes
- EGCG *not studied in breast cancer specifically
To be added in future. Let us know if you learn anything.

Loss of E-cadherin--Lobular and Ductal types only

Metastasis in lobular and invasive ductal breast cancer is characterized by loss of E-cadherin expression, which helps normal
cells maintain their organization in sheets within the tissue. Loss of e-cadherin expression contributes to the ability of the
tumor to metastsize via mesenchymal to epithelial transition (MET). Loss of E-cadherin expresion is also accompanied by
increased sEcad, which is the result of E-cadherin being broken down by MMPs. Particularly important in liver, bone, and
lung metastases.
ER+HER2-: Particularly common in Lobular type ER+HER- where it is found even at early stages without metastases. In ductal type it is
more commonly found only at an advanced stage.
TPBC: Expressed in TPBC and important to block.
HER2-Enriched: Expressed in HER2-Enriched and important to block.
TNBC: Expressed in TNBC and important to block.
Substance Notes
- Baicalein
- Curcumin
- Fisetin *may cause liver toxicity if derived from wax tree
- Fucoidan
- Lycopene
- MSM
- Reishi Mushroom Note: Reishi mushroom is an adaptogen, capable of both increasing and decreasing e-cadherin
- Vitamin D3
Overexpression of E-cadherin--Inflammatory type only
Different from other metastatic breast cancer cells where loss of E-cadherin and cell–cell attachments causes epithelial to
mesenchymal transition (EMT) increasing cancer cell invasion via single cells, IBC cells retain E-cadherin-based cell-cell
adhesions to form tumors and metastases. Therefore, contrary to other types of aggressive breast cancers, it is beneficial to
treat IBC with agents that disrupt tumor spheroids and reduce E-cadherin expression to inhibit progression.
ER+HER2-: Expressed in ER+HER2- (inflammatory type only).
TPBC: Expressed in TPBC (inflammatory type only).
HER2-Enriched: Expressed in HER2-Enriched (inflammatory type only).
TNBC: Expressed in TNBC (inflammatory type only).
Substance Notes
- Reishi Mushroom Note: Reishi mushroom is an adaptogen, capable of both increasing and decreasing e-cadherin

DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
 Evade Immune System
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be complete, may not
have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION: A well-functioning immune system is key to overcoming cancer. A low WBC count and/or a neutrophil:lymphocyte ratio above 2
indicates a dysfunctional immune system that needs support. Read more here. As cancer advances, it develops the capbility to take over the immune
system via imune infiltrating cells, which themselves drive cancer pathways.
KEY: ER+HER2- includes ER+PR+HER2- and ER+PR-HER2-, TPBC includes ER+PR+HER2+ and ER+PR-HER2+, HER2-Enriched includes ER-PR-HER2+ , and
TNBC includes ER-PR-HER2-
SPECIAL CONSIDERATIONS for ER+: Some substances may may not be appropriate for ER+ breast cancer (HER2+ or HER2-). For more information, see
ER+ Special Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.

Th1/Th2 Balance (Increase)

Response to targeted therapies requires a well-functioning immune system, and chemotherapy and radiation damage the immune system.Th1 cells
preferentially produce interferon and interleukin 2 and are the principal regulators of type 1 immunity against viral infections and tumors. NK cells are
activated by Th1-type cytokines and are particularly important because often cancer cells lose certain features in order to hide from the immune
system. However, NK cells can recognize tumor cells regardless. Interestingly, a receptor called Declin-1, which recognizes fungal infections in
normal cells, also recognizes mushrooms in cancer cells and mediates the ability of mushrooms to create NK cells against cancer cells. CR-3 is
another important receptor that recognizes beta glucans from mushrooms. Including culinary mushrooms is also important because they contain
certain components that help the immune cells recognize the medicinal mushroom extracts.

Substance Notes
- Arabinoxylose *From fermented rice bran
- Artemisinen/Artusenate
- Astragalus
- Berberine
- Beta 1,3-Glucan *From saccharomyces cerevisiae or mushrooms
- Bromelain
- Cat's Claw
- Chlorella
- Cimetidine
- Citrate
- Colostrum
- Diet No Sugar, No Dairy
- Danshen (Salvia Miltiorrhiza) *combined with Turkey Tail
- Disulfiram
Echinacea
- Fermented Wheat Germ Extract
- Garlic extract
- Ginger
- Gingko Biloba (Gingketin)
- Gynostemma
- Iodine
- IP-6
- Lactoferrin (Apo form)
- Licorice root
- Liposomal Vitamin C
- Loratadine (Claritin)
- Magnesium
- Melatonin
- Mistletoe
- Mushrooms: Reishi, Coriolus *Combination of Danshen and Turkey Tail studied in clinical trial
- Neem
- Diet No Sugar, No Dairy
- Noni
- Omega-3 EPA/DHA
- Probiotics
- Propranolol *Given perioperatively with COX-2 inhibitor, increases NK cells after cancer surgery
- Quercetin
- Shark Liver Oil
- Siberian Ginseng (Eleuthero)
- Silica
 - Silibinin/Silymarin/Milk Thistle
- Thymosin
- Tinospora Cordifolia
- Tocopherols
- Tocotrienols
- Vitamin A
- Zinc

TNF-alpha
Inflammatory chemical that helps cancer cells resist apoptosis
Substance Notes
- Andrographolide
- Apigenin
- Artemisinen/Artusenate
- Ashwagandha *can raise testosterone
- Boswellia
- Baicalein
- Danshen (Salvia Miltiorrhiza) *combined with Turkey Tail
- Curcumin
- EGCG
- Feverfew
- Ginger
- Modified Citrus Pectin (MCP)
- MSM
- Omega-3 EPA/DHA
- Panax Ginseng
- Pro-Resolving Mediators
- Reishi mushroom

Toll Receptor TLR4 (Block)

Toill receptors suppress or activate immune and inflammatory response in cancer. See Resources tab for reading suggestions.

Substance Notes
- Berberine
- Curcumin
- Danshen (Salvia Miltiorrhiza)
- EGCG
- Genistein
- Ginger
- LD Naltrexone
- Quercetin
- Resveratrol
- Sulforaphane
- Turkey Tail (Coriolus Versicolor)
Interleukins
Small proteins secreted mainly by T lymphocytes that mediate the "essential for cancer progression" interactions between cells. There are many
types: some are pro-inflammatory, some are regulatory, while others are anti-inflammatory. See Resources tab for reading suggestions.

Substance Notes
- Andrographolide *IL-1b, IL-6
- Aspirin (or willow bark) *IL-6,
- Black Seed Oil (Nigella Sativa) *IL-6
- Boswellia *IL-6, IL8
- Bromelain *IL-1b, IL-6, IL-10
- Baicalein *IL-1b, IL-6, IL-17
- Chrysin *IL-6
- Citrus Bergamot *IL-6
- Curcumin *IL-8
- Danshen (Salvia Miltiorrhiza) *IL-6
- EGCG *IL-1b, IL-6, IL-17
- Feverfew *IL-6
- Ginger *IL-6
- IV Vitamin C *IL-1b
- Luteolin *IL-6
 - Melatonin *IL-1b, IL-6, IL-12
- MSM *IL-1B, Il-6
- NSAID *IL-6, IL-8, IL-10
- Omega-3 EPA/DHA *IL-10
- Probiotics *IL-10
- Pro-resolving mediators *IL-6, IL-8, IL-10, IL-13
- Quercetin *IL-6
- Reishi mushroom *IL-1b, IL-6, IL-8, IL-11
- Vitamin D3 *IL-6, IL-10 IL-17
Parasites
Parasitic infection can dampen immune response to breast cancer and in rare cases may also contribute to development of cancer.

Substance Notes
- Artemisinen/Artusenate
- Hydroxychloroquine/Chloroquine *May not be advised with some targeted therapies; consult oncology pharmacist
- Fenbendazole
- Flubendazole
- Ivermectin
- Mebendazole
- Niclosamide
High-Mobility Group Box 1 (HMGB1)
Factor actively released by stressed/damaged cells and passively release by dying cells. HMGB1 activates macrophages, dendritic cells, and
endothelial cells, which in turn secrete more HMGB1. This driver of inflammation is highly expressed in breast cancer.

Substance Notes
- Aspirin (or willow bark) *reduced breast cancer deaths shown for early-stage tumors not Stage 4.
To be added
Immune Infiltrating Cells (IICs - TAMs, TANs, MDSCs)

Cancer takes over the immune system and continues the inflammatory signaling that typically stops in normal cells after injury resolved, such as COX-
2, VEGF, and IL-8. Common after chemotherapy and radiotherapy, which create large amounts of cellular debris. IICs include Tumor-associated
macrophages (TAMs), tumor-associated neutrophils (TANs), and myloid-derived suppresor cells (MDSCs) Major drivers of IICs are COX-2, VEGF,
EGFR, FGFR, TGF-b, HIFs, and MMP-2&9 so refer to those inhibitors as well. IICs are part of the Tumor Microenvironment summarized here.

Substance Notes
- Artemisinen/Artusenate
- Baicalein
- Dipyridamole
- Olive Polyphenols *hydroxytyrosol
- Metformin
- Modified Citrus Pectin (MCP)
- NSAID *etodolac or other prescription NSAID
- Omega-3 DHA
- Pro-Resolving Mediators *specialized lipid fractions from EPA and DHA **Take with mebendazole & Fenbendazole
- Mebendazole
- Reishi Mushroom *increased effect and reduced side effects of paclitaxel in mouse model
- Statin *Specifically Lovastatin—for TAMs
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be complete, may not
have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
 Achieve Immortality
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION: Normal cells lack an enzyme called DNA polymerase that allows the addition of more segments to the end of the
chromosome called telomeres. Cancer cells mutate a gene so they can make more of this enzyme, which allows them to avoid death and
become immortal.

KEY: ER+HER2- includes ER+PR+HER2- and ER+PR-HER2-, TPBC includes ER+PR+HER2+ and ER+PR-HER2+, HER2-Enriched includes ER-PR-
HER2+ , and TNBC includes ER-PR-HER2-
SPECIAL CONSIDERATIONS for ER+: Some substances may may not be appropriate for ER+ breast cancer (HER2+ or HER2-). For more
information, see ER+ Special Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.

Telomerase Reverse Transcriptase

Cancer cells upregulate TERT so they can continously replicate.

Substance Notes
- Baicalein
- Boswellia
- Curcumin
- EGCG
- Genistein
- Melatonin
- Pterostilbene
- Rapamycin

- Reishi mushroom

- Meditation, yoga, qigong etc *specifically meditation and chanting

- Sulforaphane
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be
complete, may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
 Avoid Death
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be complete, may not have not been verified
in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION: Most choices to encourage cancer cell death (apoptosis) are not typically recommended as standalone therapy (except IVs). Rather, they are suggested as
additions to conventional oncology treatment (chemotherapy and radiation).
KEY: ER+HER2- includes ER+PR+HER2- and ER+PR-HER2-, TPBC includes ER+PR+HER2+ and ER+PR-HER2+, HER2-Enriched includes ER-PR-HER2+ , and TNBC includes ER-PR-
HER2-
SPECIAL CONSIDERATIONS for ER+: Some substances may may not be appropriate for ER+ breast cancer (HER2+ or HER2-). For more information, see ER+ Special
Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.

Apoptosis/Cell Cycle Arrest

Directly kill the cancer cell by activating capsases.

Substance Notes
* under medical supervision
- IV Alpha Lipoic Acid *specifically Withaferin A
- Apigenin
- Ashwagandha *specifically Withaferin A

- Atovaquone*
- B17 (Amygdalin)
- Baicalein
- Betulinic acid *with chemotherapy
- Black Seed Oil (Nigella Sativa) *with chemotherapy
- Conjugated Linoleic Acid (CLA) *with Gemcitabine chemotherapy (ER+HER2- model) and in immunosuppressed TNBC model **Not for HER2+
- Danshen (Salvia Miltiorrhiza) *shown with taxol, paclitaxel, and doxorubicin (in cell lines—caution, as is CYP3A4 inhibitor)
- Dipyridamole
Echinacea
*increased effects of Paclitaxel in ER+HER2- and TNBC cells; extends lifespan of leukemic mice
- Fasting with Chemotherapy Based on clinical trials
Fenbendazole
-
Fermented Wheat Germ Extract
- *specifically TNBC
- Feverfew
- Fisetin *increased effects of cisplatin, 5-fluorouracil, and cyclophosphamide in TNBC in vitro
- Fucoidan
- Fucoxanthin
- Ginger
- Grapeseed/skin extract
- Hyperthermia*
- Itraconazole *with & w/o chemo *Caution, strong CYP3A4 inhibitor and may up-regulate autophagy
- IV Curcumin* *with chemo
- Kaempferol
- Mistletoe* *improves tolerability of chemo as well as outcomes
- Ivermectin* *Increases effectiveness of taxane chemotherapy
- Low Dose Insulin-Potentiated Chemo*
- Mebendazole* *with radiation
- Metformin*
- Moringa
- Niclosamide *with radiation
- NSAID
NSAID + Statin* *more powerful than each drug individually per Jane McLelland
- Olive Polyphenols *Improves chemotherapy effectiveness
- Omega-3 EPA/DHA
- Pomegranate (punicic acid in seeds)
- Selenium *With chemo or radiation at high dose of selenite form, 600-800 ug, not selenomethionine
- Sulforaphane
- Taurine
- Tocotrienols *Specifically gamma and delta forms, with chemotherapy
Pyroptotic cell death.
Pyroptosis is a process of programmed cell death, mediated by the key factors, GSDMD or GSDME, which can be activated by caspase-4 and/or caspase-3

- Spatholobus suberectus * in TNBC ROS-induced so avoid/inhibit glutathione

ROS (Reactive Oxygen Species)—NOT FOR TNBC during chemo/radiation

Increasing ROS inside the cancer cell limits its survival in the case of ER+, but TNBC (especially BRCA-1) appears to be dependent on ROS for survival so using
antioxidants like glutathione during chemo for TNBC may actually make the chemo more effective rather than using substances to increase ROS (listed below)

Substance Notes
 - Artemisinen/Artusenate
- Ashwagandha *specifically Withaferin A **can raise testosterone
- Black Seed Oil (Nigella Sativa) *synergistic with doxorubicin
- Carnisol
- IV Vitamin C *enhanced by HBOT immediately following
- Ivermectin
- Myricetin
- Niclosamide
- Olive Polyphenols *hydroxytyrosol (oleuropein)
- Omega-3 DHA
- Oxygen Therapies
- Selenium *Becomes oxidative only at high dose of selenite form, 600-800 ug, not selenomethionine
- Silibinin/Silymarin/Milk Thistle
- Sulforaphane
Glutathione—not for TNBC during chemo/radiation
Cancer cells use glutathione for repairing damage and resisting oxidative therapies that use ROS. Substances that block glutathione (listed below) may not be appropriate in
TNBC (especially BRCA-1) because using antioxidants (glutathione) during chemo for TNBC may actually make the chemo more effective.

Substance Notes
- Diet Low Methionine/Cysteine

- Feverfew
- Statin
- Sulfasalazine
BCL/BAX
By increasing BCL and blocking pro-apoptosis protein BAX, cancer cells become resistant to chemotherapy. The substances listed below can help reverse that process.

Substance Notes
- Anthocyanins
- Black Seed Oil (Nigella Sativa) *synergistic with doxorubicin
- Bromelain
- Capsaicin
- Feverfew
- Fucoidan
- Fucoxanthin
- Grapeseed/skin extract
- Metformin
- Olive Polyphenols
- Omega-3 DHA
- Pomegranate
- Statin
- Sulforaphane
- Tocotrienols
Cell Cycle Pathways (CDK4/6, Rb)
Deregulation of cell cycle, via the cyclin D/CDK/Rb pathway, is frequently observed in breast cancer. Drugs have been developed to target the cell cycle
control machinery, like the inhibitors of the cyclin-dependent kinases (CDK) 4 and 6. Unfortunately, resistance to these drugs commonly develops over time.
Common pathways that contribute to resistance are Rb1 (loss), PI3K, FGF, PDK1, PLK1, RANKL, and MAPK, so it's important to block these pathways when
taking CDK 4/6 inhibitors. It may be beneficial to upregulate p53 function (see Invade/Metastasize) while on CDK4/6 inhibitors. Reducing HIF-alpha-1 is also
important for improving the effectiveness of CDK4/6 inhibitors (see Invade/Metastasize). Some natural substances have been shown in in vitro studies to
inhibit CDK4/6 but this research has not necessarily been extended to animal studies. These substances are not presented as replacements for CDK4/6
inhibitor drugs but as possible enhancements or additions to other therapies.
ER+HER2-: Luminal tumors are generally characterized by an enhanced expression of cyclin D, via estrogen receptor activation. Drugs approved to block CDK 4/6 include
palbociclib, ribociclib, and abemaciclib.
TPBC: Luminal tumors are generally characterized by an enhanced expression of cyclin D, via estrogen receptor activation. CDK 4/6 blocking drugs are in clinical trials for
TPBC. Unlike ER+HER2- cells, ER+HER2+ cancer cells upregulate glycolysis when exposed to CDK4/6 inhibitors, pointing to the need to strongly block glycolysis (IVC?)
when on that therapy.
HER2-Enriched: cell cycle mutations are found in about 50% of HER-Enriched tumors (see fig. 3 of ref) but no drugs are currently approved.
TNBC: cell cycle mutations are found in about 50% of TNBC tumors (see fig. 3 of ref) but no drugs are currently approved.

Please refer to the following pathways, which should be blocked as they contribute to resistance to CDK4/6 inhibitor drugs, which include palbociclib, ribociclib,
and abemaciclib: Bcl-2, FGFR, Akt/mTOR (PTEN), IGF, MAPK, HER2, and Rb. Drugs are being developed to block these pathways for those who have
experienced resistance, but anyone who is taking a CDK 4/6 inhibitor should consider adding substances from these pathways into the protocol to reduce the
risk of resistance.
- Ashwagandha *specifically Withaferin A **can raise testosterone ***shown in ER+HER2- and TNBC cell lines
- Baicalein *blocks PLK1, which is involved 4/6 inhibitor resistance
- Honokiol *shown in gastric cancer and prostate cancer cell lines
Licorice root
- *shown in NSCLC cell lines
Sulforaphane
- *shown in ER+HER2- and TNBC cell lines
In progress--more to be added

Ferroptosis
 Ferroptosis takes advantage of cancer's sequestering and storage of iron. Ferroptosis is dependent upon intracellular iron, but not other metals, and is
morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy.
The pathways and blockers shared below were summarized by breast cancer patients who read Jane McLelland's How to Starve Cancer chapter on Ferroptosis, integrative
cancer practitioner sources and research on Pubmed.
Important: Please visit the separate Sheet on the Ferroptosis protocol, which details dietary strategies, additional resources, clinics, and a more intensive dietary and detox approach to
Ferroptosis offered by the late Dr. Etienne Callebout.

DIET LIMITATIONS: Please visit this separate sheet with more information on the Ferroptosis protocol.

SUBSTANCES TO USE (choose one or two drugs/supplements under each category)

Inhibit HDAC (Protect neurons)
- Beta Hydroxybutyrate
- Sodium phenylbutyrate
- Valproic Acid
Inhibit NRF2
- Fenugreek (Trigonelline) *Look for supplement standardized to Trigonelline/fenusides
- Ibuprofen *Brain mets
Inhibit Thioredoxin reductase 1 (TrxR1)
- Piperlongumine *Warning-inhibits CYP3A4
- Hydroxycitrate (Garcinia Cambogia) *Gambogic acid
- Auranofin *Prescription medication
- Rabdosia rubescens *Isoferritin A (c)--from Rabdosia rubescens (Dong Lin Cao)
Inhibit STAT3
- MSM
- PEITC *Phenethyl isothiocyanate from watercress *Inhibits GTX4
- Feverfew *Parthenolide
- Fisetin
- Metformin
- Niclosamide
Inhibit mTOR (Increase autophagy)
- Artemisinen/Artusenate *Increases intracellular iron *Produces H2O2 free radicals
- Ginger *Standardized to 6-gingerol
- Metformin
Inhibit NADPH-dependent CoQ10
- Statin *Simvastatin, Lovastatin, Atorvastatin
Inhibit NADPH via G6PD/6PGD
- IV Vitamin C *Produces H2O2 free radicals
- Ketotifen *Asthma medication by prescription
- Methotrexate
- Syrian Rhubarb *Specifically chrysophanol for glutathione Peroxidase and Physcion (Parietin) to block G6PD. Oral cancer
Inhibit xCT cysteine glutamate antiporter/lower glutathione *Also Sorafinib, a chemotherapy medication
- Feverfew *Parthenolide
- Piperlongumine *Warning-inhibits CYP3A4
- Sodium selenite
- Sulfasalazine *Only use on IVC days or for a few days during kill phase
Boost xCTR inhibition by increasing ROS (use if basic approach not enough)
- Garlic extract
Block cysteine. *Also cisplatin, a chemotherapy drug
- Feverfew *Parthenolide
- Cysteinase (PDAC)
Inhibit GPX4 (warning: increases exosomes - use CBD to inhibit). *Also Altretamine, an ovarian cancer drug
- PEITC
- Ashwagandha *Specifically Withaferin A, a withanolide found in ashwagandha
- Danshen (Salvia Miltiorrhiza) *Cryptotanshinone, dihydrotanshinone. Warning: CYP3A4 inhibitor
- Statin *Lipophilic statins
- Heteronemin
- RSL3
- Curcubitacin B
- Syrian Rhubarb *Specifically chrysophanol for glutathione Peroxidase and Physcion (Parietin) to block G6PD. Oral cancer
- Leflunomide *Low dose. * Blocks DHODH, which regenerates CoQ10 * Synergy with sulfasalazine
Disrupt microtubules
- Clemastine *Old antihistamine, best added to Mebendazole
- Fenbendazole *Not listed in book "How to Starve Cancer"
- Mebendazole *Suppresses p-gp to retain chemo inside cells
Block FPSP1 *Keeps cancer from rewiring metabolism to avoid being killed by ferroptosis
- Statin
Block DHODH (regenerates CoQ10)
- Leflunomide *Synergy with sulfasalazine
Inhibit glutathione-s-transferase
- Artemisinen/Artusenate
- Nitazoxanide
Block ferroptosis escape routes. Cisplatin, Lapatinib, Neratinib, Sorafenib (chemotherapy and TKI medications)
Modulate haem oxygenase-1 (HO-1). *Also oncology drug Lapatinib
- Andrographolide *Andrographis
- Acetominophen
- Gingko Biloba (Gingketin) *NSCLC
Modulate ACSL4
- Bromelain
- Conjugated Linoleic acid (CLA)
- Danshen (Salvia Miltiorrhiza) *Cryptotanshinone, dihydrotanshinone. Warning: CYP3A4 inhibitor
- Aspirin (or willow bark) *HCC
Inhibit glutathione-s-transferase
- Artemisinen/Artusenate *Malaria medication
- Nitazoxanide
Inhibit transferrin and ferroportin
- Butcher's broom *Ruscogenin
Increase lyposomal permeability
- Sirasemine
- Clemastine
- Disulfiram
Increase intercellular iron
- Artemisinen/Artusenate
- Salinomycin (Ironomycin)
- Garlic extract
- Lactoferrin (Holo form) *NOT Apo-Lactoferrin, typically found in lactoferrin supplements **May not be available
Inhibit estrogen receptor
- Metformin
- Danshen (Salvia Miltiorrhiza) *Cryptotanshinone, dihydrotanshinone. Warning: CYP3A4 inhibitor
Increase H2O2 free radicals
- IV Vitamin C
- Artemisinen/Artusenate
Stimulation of 15-lipoxygenase
- Ibuprofen *Brain mets
Block serine synthesis
- Disulfiram *Take SOD-1 (superoxide dismutase) to break down superoxide to H2O2 + O2 and avoid damage to tissues.
- Superoxide Dismutase *SOD1
Inhibit gamma-glutamyl cycle
- Rabdosia rubescens *Also called Donglingcao, a Chinese herb or Oridonin
Inhibit exosomes *Inhibiting GPX4 causes an increase in iron-containing exosomes
- CBD (from Cannabis) *not THC
- Statin *Inhibits cholesterol needed by exosomes
Activate VDAC2/3 *All inhibitors from Jeffery Dach's book "Cracking the Code." However, he only describes VDAC activation in general, not 2/3 specifically)
- Aspirin (or willow bark)
- CBD (from Cannabis)
- Fenofibrate
- Itraconazole
- Metformin
Inhibit Stearoyl-CoA Desaturase (SCD1) *Especially if tumor has TP53 or BAP1 mutation
- Niacin (Nicotinic acid)
Inhibit transsulfuration/lower homocysteine to <15
- Diet Low Methionine/Cysteine
- Tri-Methyl Glycine (TMG) *Betaine Anhydrase 50mg/kg bid
- Folate (5-MTHF)
- Vitamin B6
- Vitamin B12 (methylcobalamin)
- Choline
Inhibit CAIX *From Dr. Daniel Thomas
- Spermidine *An experimental; drug, SLC-0111, is derived from spermidine
- Fermented wheat germ extract
Suppress P-Glycoprotein pump (P-gp) *P-gp pushes chemo out of cells
- Mebendazole
Remove Excess Ferritin after IVC if needed *Get ferritin level checked after IVC
- Deferoxamine
- Baicalein *Baicalein (Scutellaria baicalensis). Stops ferroptosis for 48 hrs; use after IVC only at end of ferroptosis
cycle.
SUBSTANCES TO AVOID *Refer to Ferroptosis protocol for dietary guidance/foods to avoid

Stop 48 hours before Ferroptosis

AVOID antioxidants
- Tocopherols *Vitamin E
- Tocotrienols *Vitamin E
- CoQ10 *Ubiquinol, ubiquinone
- IV Alpha Lipoic Acid *ALA, any form
- Melatonin *Low dose OK for sleep (controversial as high-dose melatonin has been shown to synergize w/ chemo/radiation)
Riordan Clinic recommends high-dose melatonin with IVC so this advice from JM may be misguided.
AVOID iron/copper chelators
 - IP-6
- Curcumin
- Tetrathiomolybdate (TM)
- EGCG *Green tea
- IV Alpha Lipoic Acid
- Baicalein *Baicalein
- Lactoferrin (Apo form)
AVOID polyphenols
- Quercetin
- Luteolin
- Genistein
AVOID NRF2 activators/increase glutathione
- DIM/I3C
- Resveratrol
- Sulforaphane
- Cordyceps
- Pomegranate
AVOID autophagy inhibitors
- Dipyridamole
- Hydroxychloroquine/Chloroquine
- Pyrvinium pamoate
- Amiloride (Midamor)
- Extra Virgin Olive Oil *Containing oleacanthol
- Black seed oil (Nigella sativa)
AVOID glutaminolysis inhibitors *Also l-asparaginase, which is marketed as a drug top treat acute lymophoicytic leukemia
- EGCG *Green tea **Can be taken at low dose because it triggers ROS
Curcumin + Ursolic Acid
Resveratrol + Ursolic Acid
- BPTES
AVOID lipid peroxidation inhibitors
- Selenium
- Tocopherols *Vitamin E
- Tocotrienols *Vitamin E
- Cinnamon (not culinary)
- Chrysin *Take in starve phase to reduce HIF-1
- Pawpaw *Take in starve phase to reduce HIF-1
- Noscapine *Found in over-the-counter cough medicines. Take in starve phase to reduce HIF-1
- THC (from Cannabis) *Pure CBD ok
- Boswellia
- Honokiol
AVOID H2O2 free radical inhibitors
- Doxycycline
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be complete, may not have not been verified in
humans, and is not meant as medical advice but as a guide to further exploration.
 this page is under construction March 2022
Gene Mutations
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be complete, may not have not been
verified in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION:

KEY: ER+HER2- includes ER+PR+HER2- and ER+PR-HER2-, TPBC includes ER+PR+HER2+ and ER+PR-HER2+, HER2-Enriched includes ER-PR-HER2+ , and TNBC includes
ER-PR-HER2-
SPECIAL CONSIDERATIONS for ER+: Some substances may may not be appropriate for ER+ breast cancer (HER2+ or HER2-). For more information, see ER+ Special
Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.

p53 tumour suppressor gene (protect and re-boot)

Common in most difficult-to-treat cancers. Mutation leads to loss of protection by silencing tumor suppressor gene. Cells with a normal p53 gene respond to
genotoxic stress by either repairing the cell or causing apoptosis. If the gene is mutated, the abnormal cell is allowed to live.
Substance Notes
- Curcumin
- EGCG
- Folate (5-MTHF)
- Garlic extract
- Genistein
- Grapeseed/skin extract
- Honokiol
- Melatonin *possibly avoid in tumors with p53 mutation
- Quercetin
- Resveratrol
- Silibinin/Silymarin/Milk Thistle
- Resveratrol
- Vitamin C
PTEN tumour suppressor gene (protect and re-boot)
PTEN opposes activation of the PI3K/Akt/mTOR pathway, the gatekeeper for tumour growth. PTEN has an up-regulating feedback loop with tumor suppressor gene
p53 and prolongs the half-life of the p53 protein, enhancing genomic and centromere stability. PTEN down-regulates VEGF expression and IGF-1 signalling, and it
modulates G2/M cell-cycle arrest. Up-regulated NfKB suppresses PTEN function so important to block NfKB. PTEN function can be reduced by deletion, mutation or
epigenetic silencing. It is very sensitive to small chromosomal rearrangements, and is often inactivated when BRAC-1 mutations reduce DNA repair. For more
information see Dr. Neil McKinney's textbook here or here.
Substance Notes
- Ashwagandha
- Astragalus
- Baicalein
- Beta Hydroxybutyrate
- Black Seed Oil (Nigella Sativa)
- Curcumin
- DIM/I3C
- EGCG
- Genistein
- Grapeseed/skin extract
- Honokiol
- Melatonin
- Omega-3 DHA
- Quercetin
- Resveratrol *Combination of resveratrol + curcumin shown to be effective in animal model of prostate cancer.
- Silibinin/Silymarin/Milk Thistle
- Resveratrol

MYC (inhibit)
Most common proto-oncogene and influences all Hallmarks as well as tumor microenvironment. Directly targets an enzyme that turns on the Warburg effect. Per
McKinney, MYC drives CSCs and is inhibited by berberine, curcumin and grapeseed proanthocyanins
Substance Notes
- Baicalein
- Berberine
- Curcumin
- Grapeseed/skin extract
Ras (inhibit)
Very common proto-oncogene and earliest mutation in cancer cells. Ras-raf pahway. Turns on and off signals between cell surface and nucleus, keeping them in
the on position.
 Substance Notes
- Honokiol
#N/A
#N/A
#N/A
Src (inhibit)
Oncogene that is a key messanger in many important cellular pathways regulating proliferation, differentiation, survival, motility, and angiogenesis including MAPK,
STAT3, osteoclast formation and survival (bone mets), and VEGF. It's driven by a number of signals upregulated in cancer including colony stimulating factor (CSF),
PDGF, RANKL, the tyrosine kinases including EGFR, and HER2, IL6, Integrins, and VEGF. src appears to play a role in regulating Estrogen receptors and plays a
key role in the transformation of the dormant tumor cells to active cancer cells. Pharma drugs to block src are in Phase I and II trials with other targeted therapies.
Substance Notes
- Baicalein
#N/A
#N/A

HDAC - histones (inhibit)

Substance Notes
#N/A
#N/A
#N/A

Per Herbalist Kerry Bone, Ginkgo is important for increasing genomic stability in the face of cellular damage from radiation. Other nutrients with human clinical trial
data showing they increase markers of genomic stability: folate, B12, zinc, B3, green tea (EGCG), mediterranean diet plus CoQ10, korean ginseng, broccoli, selenium,
and magnesium.
 Eliminate Cancer Stem Cells
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not be complete,
may not have not been verified in humans, and is not meant as medical advice but as a guide to further exploration.
DESCRIPTION: The tumor seeds its microenvironment and the neighboring tissue with cancer stem cells (CSCs) that lay dormant and are not
affected by chemotherapy or radiation therapy. Instead, they wait for the body to send signals to begin growing, especially after surgery and
highly oxidative therapies like chemotherapy and radiation. Hypoxia-inducible factor 1 (HIF1) is upregulated during oxidative therapies and
maintains a tumor microenvironment that is conducive to maintaining cancer stem cells. (See the Invade/Metastasize tab for substances to
block HIF1.) CSCs have the ability to migrate to other organs and begin replicating to form new tumors. CSCs also have an enhanced ability to
gain mutations and create a more aggressive cancer cell type when cancers metastasize. To learn more about the Tumor Microenvironment,
go here. Many herbs can downregulate the Translationally Controlled Tumor Protein (TCTP), which is upregulated in cancer cells and affects
p53 tumor suppressor function, to convert CSCs back to normal stem cells.
SPECIAL CONSIDERATIONS for ER+: Some substances may not be appropriate for ER+ breast cancer (HER2+ or HER2-). For more information,
see ER+ Special Considerations
TYPICAL DOSAGES: For additional Information on substances and typical clinical dosing click here.
REFERENCES: COMING IN FUTURE.
In a recent paper reviewing the literature, McKee and Naujokat (2020) listed the “Big Five” phytochemicals for targeting CSCs. These
substances are multitaskers and several pathways and growth factors (Notch, Wnt/b-catenin, Hedgehog, NFkB, and STAT-3, TGF-b and HIFs),
which are important for promoting the transition of cancer stem cells to mature cancer cells. The “Big Five” are Sulforaphane, Curcumin,
Resveratrol, EGCG, and Genistein. In vitro studies indicate many substances have activity against CSCs. Including several of these in an
integrative cancer protocol both blocks various pathways and kills CSCs. These are listed below.
Substance Notes
- Anthocyanins *red & blue fruits/veg
- Apigenin
- Artemisinen/Artusenate *via downregulating TCTP
- Ashwagandha *can raise testosterone; specifically studied Withaferin-A extract
- Aspirin (or willow bark)
- Baicalein
- Berberine
- Beta Carotene
- Black Seed Oil (Nigella Sativa)
- Boswellia *Should include AKBA form
- Burdock (Arctigenin)
- CBD (from Cannabis)
- Curcumin
- Danshen (Salvia Miltiorrhiza)
- Daidzin (soybean)
Dandelion
- DIM/I3C
- Doxycycline *Combination of Doxycycline + Azithromycin + IV Vitamin C also studied
Echinacea
- EGCG
- Fenbendazole
- Fermented Wheat Germ Extract
- Feverfew
- Fisetin *may cause liver toxicity if taken for extended period
- Flubendazole
- Genistein
- Ginger
- Gingko Biloba (Gingketin)
- Grapeseed/skin extract
- Hesperetin
- Honokiol
- Hydroxychloroquine/Chloroquine *May not be advised with some targeted therapies; consult oncology pharmacist
- Ipriflavone
- Ivermectin
- Luteolin
- Lycopene *take with oil-based products such as Black Cumin Seed Oil or Omega-3
- Mebendazole
- Melatonin
- Metformin *Take a B12 supplement while on Metformin as it depletes B12
- MSM
- Narigenin *found in citrus bergamot along with Hesperitin
- Niacin (Nicotinamide)
- NSAID
- Olive Polyphenols *oleuropein and hydroxytyrosol
- Omega-3 DHA
- Panax Ginseng
- PEITC
- Piperine
- Pomegranate
- Propranolol
- Pterostilbene
- Quercetin
- R-Alpha Lipoic Acid (no 'S' )
- Reishi mushroom
- Resveratrol
- Salinomycin (Ironomycin)
- Schisandra
- Silibinin/Silymarin/Milk Thistle
- Sulfasalazine
- Sulforaphane
- Tocopherols *gamma and delta only
- Tocotrienols
- Turkey Tail (Coriolus Versicolor)
- Ursolic Acid
- Vitamin A
- Vitamin D3
A number of pathways, oncogenes, and overexpressed proteins contribute to the promotion of cancer stem cells.
HIF1
MYC oncogene
akt/mTOR
Wnt/beta-catenin
TGF-b
PPAR-Gamma
NFkB
PTEN
P-Glycoprotein transporter
IL-6 and IL-8 inflammatory markers
STAT3
DISCLAIMER: This information was gathered from published research in cell lines or animals or from typical clinical use, may not have not
been verified in humans, and is not meant as medical advice.
Reading Suggestions & Resources

EFT/tapping can support our capacity to take in what we need to, and let go of what we don't need. Learn quick tools to move stressful feelings & thoughts
fast. Devorah had metaplastic carcinoma a rare form of breast cancer and now she is thriving and busy creating and sharing powerful tools that can quickly
support others in treatment to shift our brain state from “fight/flight" back to "calm/curious".
https://myhealingcommunity.com/devorah-tools-for-the-wait/

Endocrine Resistance in Hormone Receptor Positive Breast Cancer–From Mechanism to Therapy. 24 May 2019
https://www.frontiersin.org/articles/10.3389/fendo.2019.00245/full

Care Oncology Center (COC) Scientific References for Metformin, Statins, Mebendazole, and Doxycyline
https://careoncology.com/the-coc-protocol-in-breast-cancer/ref/2/?
fbclid=IwAR2Vk4oeZSTqMGqwue0AtdWFK0Ma1KYLH1PhNuoOvBXmBrMUiZnTlHlAUZM_aem_AW88tsIMSszycVg747ZfWKh8zEWM_fW2lp3diHfLIu59oZRVH
Eqvg6ONpmN0UzfDL6qTqL9-DHyDJzD-eBN07bpX6TIbFDfMzJL6kDh4vHoC6RF6vZH9IEoDP3CsM-Zgaz0

Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969803/

Metabolism-Based Therapeutic Strategies Targeting Cancer Stem Cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438930/

Natural Compounds as Regulators of the Cancer Cell Metabolism

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670510/?fbclid=IwAR3fawvIO3xGlyX_YtWWzMTdsYz77A0eZsTnzij696gafMXEkGPCIerOBY8

A broad-spectrum integrative approach for cancer prevention and treatment

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4819002/

Rethinking the War on Cancer (read full paper at sci-hub.se on a computer, not mobile device)
Note: For context, it is important to read the earlier papers by Hanahan and Weinburg (2000 and 2011), which Hanahan cites in this paper.
https://pubmed.ncbi.nlm.nih.gov/24351321/

Hallmarks of Cancer: New Dimensions

https://cancerdiscovery.aacrjournals.org/content/12/1/31?fbclid=IwAR3EzdSBAmnFfWxWpRIBep8xbFgP8Q5QD8aba_923vgW1RIxMj2-29Hslro

Books:

How to Starve Cancer by Jane McLelland

https://www.amazon.com/How-Starve-Cancer-Jane-McLelland/dp/0951951734

The Metabolic Approach to Cancer by Nasha Winters

https://www.amazon.com/Metabolic-Approach-Cancer-Integrating-Bio-Individualized/dp/1603586865/ref=sr_1_1?
keywords=the+metabolic+approach&qid=1572739555&s=books&sr=1-1

Life Over Cancer: The Block Center Program for Integrative Cancer Treatment
https://www.amazon.com/Life-Over-Cancer-Integrative-Treatment/dp/0553801147

Naturopathic Oncology – An Encyclopedic Guide For Patients & Physicians

https://www.drneilmckinney.ca/product-category/books/ (pdf, or hard copy in Canada only) https://www.amazon.com/Naturopathic-Oncology-Encyclopedic-
Patients-Physicians/dp/1926946154/ref=pd_lpo_1?pd_rd_i=1926946154&psc=1 ) (US hard copy). For hard copy in other countries, check your Amaxon online
retailer.

Definitive Guide To Cancer by Lise N. Alschuler, Karolyn A. Gazella

https://www.amazon.com.au/Definitive-Cancer-Gazella-Karolyn-Alschuler/dp/1587613581

Online Learning Resources:

Our Healing Cancer Study Support Group and Starve Breast Cancer Study Group: FREE
www.myhealingcommunity.com

HER2+ Metro Mavens Facebook Group (HER2+ support group—join by sending friend request + message to Maria Wessling Bachteal)
https://www.facebook.com/groups/2209107679144037/

How to Starve Cancer Online Course by Jane McLelland: $97

https://how-to-starve-cancer.teachable.com/p/how-to-starve-cancer-online-course

The Path of Breast Cancer Online course by Carol Lourie, ND

https://carollourie.com/prelaunch-the-path-of-breast-cancer/

Beyond Conventional Breast Cancer Therapies Website and Resources

https://bcct.ngo/cancers-and-symptoms/cancer-handbooks/breast-cancer

Living Beyond Breast Cancer

http://www.lbbc.org

Cancer Treatments: From Research to Application (Daniel Stanciu, Ph.D.)

http://cancertreatmentsresearch.com

Believe Big (Integrative cancer treatment information with emphasis on mistletoe therapy and practitioner directory)
http://believebig.org

The Tumor Microenvironment and Its Importance in Cancer Pathways

https://docs.google.com/document/d/1AGI30DBakw3od58YKuHF6fE2-4gVpACjHKo0feKhanM/edit?usp=sharing

Interleukins (ILs) Articles: to be better integrated into existing Evade Immune System page on this worksheet..in future

Interleukins Associated with Breast Cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324869/#:~:text=Interleukins%20are%20now%20proven%20to,survival%20rates%20of%20breast%20cancer.

IL-6 Receptor Inhibitor Suppresses Bone Metastases in a Breast Cancer Cell Line
https://link.springer.com/article/10.1007/s12282-018-0853-9

IL-8 Identified as Estrogen Receptor-Regulated Factor Involved in Breast Cancer Invasion and Angiogenesis by Protein Arrays
https://link.springer.com/article/10.1007/s12282-018-0853-9

IL-10 Unique Therapeutic Agent, Simultaneously Stimulates Antitumor Immunity & Inhibits Tumor-Associated Inflammation.
https://pubmed.ncbi.nlm.nih.gov/24778315/

Molecular Pathways: IL11 as a Tumor-Promoting Cytokine—Translational Implications for Cancers

https://aacrjournals.org/clincancerres/article/20/22/5579/117468/Molecular-Pathways-IL11-as-a-Tumor-Promoting

IL-17 Could Promote Breast Cancer Progression at Several Stages of the Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691460/

IL-4 and IL-13 are Elevated in TAMs, which Produce High Levels of Il-10
https://www.hindawi.com/journals/njos/2014/271940/

Soluble interleukin-6 receptor is a prognostic marker for relapse-free survival in estrogen receptor-positive breast cancer
https://pubmed.ncbi.nlm.nih.gov/23902164/

Specialized Pro-resolving Mediators: Endogenous Regulators of Infection and Inflammation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242505/

Stromal cell-laden 3D hydrogel microwell arrays as tumor microenvironment model for studying stiffness dependent stromal cell-cancer interactions
https://pubmed.ncbi.nlm.nih.gov/29653286/
Substances that modulate interleukin activity:
Aspirin (IL-6)
Boswellia (IL-6, IL-8)
Bromelain (IL-1b, IL-6, IL-10)
Baicalein (IL-17)
Black Seed Oil (IL-6)
IV Vitamin C (IL-8)
NSAIDs (IL-1b)
Curcumin (IL-6, IL-8, IL-10)
Omega-3 EPA/DHA (IL-10)
Feedback
Vitamin D3 (IL-6, IL-10 IL-17) is most welcome. Please use this form: https://forms.gle/117vEji1uagkD9bg9
Bergamot (IL-8)
R
[1] Haritaki is referred to as: TERMINALIA CHEBULA: https://www.researchgate.net/profile/Prakash-Gupta-
20/publication/279651727_Biological_and_pharmacological_properties_of_Terminalia_chebula_Retz_Harit
aki_-_An_overview/links/56f4ad6708ae38d7109f6dca/Biological-and-pharmacological-properties-of-
Terminalia-chebula-Retz-Haritaki-An-overview.pdf