Recent advancement in cancer and diabetes 2024.pptx
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The document discusses recent advancements in cancer and diabetes treatments, highlighting innovative approaches like bacteriotherapy, microRNA therapy, hyperthermic intraperitoneal chemotherapy (HIPEC), and novel drug delivery systems such as polymeric nanoparticles and aptamers. It also details new diabetes therapies, including smart insulin, artificial pancreas systems, and SGLT2 inhibitors, emphasizing their benefits for blood glucose control and patient adherence. Overall, it presents a comprehensive overview of cutting-edge therapeutic strategies aimed at improving patient outcomes in cancer and diabetes management.
Recent advancement in cancer and diabetes 2024.pptx
- 1. Recent advancements in the treatment of Cancer and Diabetes Anagha R Anil M.Pharm Pharmacology
- 3. RECENT ADVANCEMENTS IN CANCER THERAPY Cancer Therapy Bacteriotherapy MicroRNA HIPEC Drug Delivery Systems Aptamers Polymeric nanoparticles Ribosomal Targeting Others Minimally invasive surgery
- 5. 1. Vehicles to deliver anti-cancer agents • Anaerobic bacteria can bypass traditional chemotherapy obstacles and thrive in the hypoxic tumor environment, making them potential candidates for precision local tumor targeting. • Bacteria can be engineered to carry siRNA to target specific cancer genes. • For example, cisplatin-resistant ovarian cancer cells were treated with engineered Salmonella typhi carrying siRNA against MDR1, followed by cisplatin. This approach reduced MDR1 levels and slowed tumor growth in mice.
- 6. 2. Bacteria mediated immune boosting • Bacteria like E. coli are drawn to the hypoxic environment of tumors. • Bacterial infections can produce pathogen-associated molecular patterns (PAMPs) and release heat shock proteins (Hsp70) from necrotic cells. • Hsp70 aids for strong antigen-specific immune responses. • PAMPs have conserved motifs that are recognized by pattern-recognition receptors (PRRs), initiating complex signaling cascades that trigger host immune functions(develops CD4+ and CD8+ T cell).
- 7. 3. Bacterial biofilm to curb cancer metastasis • Biofilms are structures formed by an assembly of microorganisms embedded in an extracellular polymeric matrix. • These structures enable bacteria to stick to each other and create a nutrient-limited environment around cancer cells, thus can hinder cancer cell growth and spread. • Example: Streptococcus agalactiae biofilm can prevent cancer cells from adhering to endothelial cells, a critical step in cancer metastasis.
- 8. 4. Release bacterial peptides that target carcinomas • Nonribosomal peptides (NRPs) are bioactive metabolites produced by bacteria, cyanobacteria, and fungi. Key Peptides: • Azurin: Produced by Pseudomonas aeruginosa, azurin shows cytotoxic effects against various cancer cell lines, including breast carcinoma and colon cell lines. The p28 domain of azurin enters cancer cells via receptor-mediated endocytosis, inhibits angiogenesis by affecting VEGFR-2 tyrosine kinase and bFGF (FGFR-1), and forms a complex with p53 to inhibit cell proliferation. • Nisin: This peptide creates pores in the tumor cell membrane, disrupting ion homeostasis and triggering apoptosis. Nisin can inhibit genes involved in cancer metastasis, such as MMP2, CDTs, and MMP9.
- 9. MicroRNA
- 10. MicroRNA 1. In the nucleus, miRNA Genes are transcribed by RNA polymerase II to produce primary miRNA (pri-miRNA) transcripts. 2. Drosha and DGCR8: These proteins process pri-miRNA into precursor miRNA (pre-miRNA). 3. Exportin-5 transports pre-miRNA from the nucleus to the cytoplasm. 4. Dicer, an enzyme that cuts pre-miRNA into a 20-22 nucleotide miRNA/miRNA* duplex. 5. The miRNA duplex is loaded onto the RNA-induced silencing complex (RISC), where the duplex separates into mature single-stranded miRNA. 6. Mature miRNA in the RISC complex binds to complementary sequences on target mRNA. 7. Depending on the complementarity, RISC either degrades the mRNA or inhibits its translation, leading to decreased protein production. Eg: miR-15a and miR-16-1: These miRNAs suppress cyclin genes (CCND1, CCNE1) and the Bcl-2 gene, inducing cell cycle arrest and apoptosis.
- 11. HIPEC - Hyperthermic Intraperitoneal Chemotherapy • Hyperthermic intraperitoneal chemotherapy (HIPEC) combines cytoreductive surgery (CRS) with heated chemotherapy, providing both pharmacokinetic and cytotoxic advantages. • Hyperthermia can reduce adverse effects of chemotherapy drugs and enhance drug penetration into tissues. • Drugs used in HIPEC should have a heat-synergistic cytotoxic effect and act independently of the cell cycle. • HIPEC requires a device to warm and circulate chemotherapy solution to maintain constant peritoneal cavity temperature. Limitations: • Lack of established HIPEC chemotherapy regimen, treatment duration, and temperature standards.
- 12. • The addition of HIPEC with cisplatin to cytoreductive surgery in stage III ovarian cancer resulted in recurrence-free survival that was longer by 3.5 months and overall survival that was longer by nearly a year than surgery alone and did not result in higher rates of side effects.
- 14. Aptamers • Aptamers are small, single-stranded DNA or RNA molecules that form unique three-dimensional structures, allowing them to bind specifically to various targets, such as proteins, toxins, and cells. • CTLA-4 and PD-1 proteins are expressed on T-lymphocytes and act as immunological checkpoints. • They help regulate immune responses, but their interaction raises the signal threshold required for T-cell activation, resulting in signals that inhibit T-cell responses. • By blocking the CTLA-4 signal, aptamers can enhance T-cell activation and proliferation, which is beneficial for cancer immunotherapy. • Eg: AS1411 Aptamer: Can enter the nucleus, binding to nucleolin and inhibiting Bcl-2 tumor genes, preventing cancer cell escape from apoptosis.
- 15. Polymeric nanoparticles • Polymeric nanoparticles (PNPs) are advanced drug delivery systems designed to target cancer cells specifically while minimizing damage to surrounding healthy cells. • PNPs can be engineered to specifically target cancer cells, reducing the impact on healthy cells. • They allow for controlled and sustained release of drugs, enhancing the efficacy of the treatment. • Due to their small size, PNPs can passively accumulate in tumor tissues through the EPR effect, where they penetrate the leaky vasculature of tumors and retain there. Eg: Poly (lactide-co-glycolide) (PLGA): salinomycin-loaded PLGA nanoparticles target CD133+ osteosarcoma cancer stem cells, significantly improving treatment efficacy.
- 16. Ribosomal Targetting • Dysregulation of ribosome biogenesis has been observed in many tumor cells, leading to altered protein synthesis levels, which are crucial for cancer cell growth and proliferation. • In cancer cells, the inhibition of RNA Pol I, which is responsible for ribosomal RNA (rRNA) synthesis, can lead to the release of RPL5 and RPL11 from the nucleolus. This release stimulates p53 activity, which is essential for inducing cell cycle arrest or apoptosis. • CX-3543, an inhibitor of Nucleolin, has shown promise by suppressing rRNA transcription and inducing apoptosis through p53 activation.
- 18. Minimally invasive surgery • Surgical procedures that limit the size of surgical incisions needed so that the blood loss, wound healing time, associated pain and scarring, hospitalization time, risk of infection, and postsurgical complications are usually much less. • Neoplasms such as early gastric cancer, colon cancer, and esophageal cancer are now preferentially approached with minimally invasive surgery with decreased pain, lower wound infection rates, better postoperative pulmonary function, and shorter recovery time compared with traditional laparotomy.
- 19. New therapeutic agents and novel drug target
- 21. RECENT ADVANCEMENTS IN DIABETES THERAPY T1D Digital health management Smart insulin Artificial pancreas Stem cell therapy T2D GLP-1 receptor agonist SGLT2 inhibitors GLP-1 AND GIP DUAL AGONIST (TIRZEPATIDE)
- 22. ● Provides benefits like better glycaemic control, reduced risk of hypoglycaemia, and increased patient convenience. ● Aims to eradicate the need for multiple daily injections by developing long-acting formulations that adjust insulin release based on glucose levels over time. ● Potential to reduce the burden of frequent injections, improving patient adherence and quality of life. Smart Insulin ● A new class of insulin analogs intended to mimic the body’s natural insulin secretion in response to glucose levels. ● Designed to self-regulate insulin release based on an individual’s blood glucose level. ● Glucose responsive insulin formulations contain glucose-sensing elements triggering insulin release in response to hyperglycaemia.
- 23. • A randomized clinical trial of 16 weeks showed improved glycaemic control in T1D children using an artificial pancreas system. • Long-term clinical trials demonstrated improved glycaemic control and reduced risk of hypoglycaemia in adults with T1D over six months. Artificial Pancreas • Integrates a continuous glucose monitor, an insulin pump, and a control algorithm to regulate insulin delivery based on real-time glucose measurements. • Eg: MiniMed 670 G by Medtronic and the t: slim X2 insulin pump with Control-IQ Technology by Tandem Diabetes Care • A pioneer study in 2005 reported improved glycaemic control and reduced occurrence of hypoglycaemia in children with T1D after using an artificial pancreas system.
- 24. Stem Cell Therapy ● Stem cell therapy aims to rejuvenate insulin-producing β-cells in the pancreas using stem cells. ● Insulin-Producing Cells (IPCs) from iPSCs(induced pluripotent stem cells) ● Mesenchymal stem cells (MSCs) can differentiate into IPCs using similar protocols as iPSCs, involving stepwise induction of endoderm and pancreatic progenitors. ● Generation of Islet Organoids from Pluripotent Stem Cells (ESCs/iPSCs): Islet organoids mimic pancreatic islets' structure and function, derived from ESCs or iPSCs. ● Generation of Islet Organoids from Multipotent Stem Cells: can form islet organoids when induced to pancreatic endodermal cells and co-cultured with supporting cells in 3D systems. ● Bioengineered scaffolds support stem cell differentiation into functional β-cells by mimicking pancreatic ECM. They can enhance cell survival and function post-transplantation.
- 27. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, also known as gliflozins, are a class of antidiabetic drugs that reduce renal tubular glucose reabsorption, which lowers blood glucose without stimulating insulin release. SGLT2 inhibitors work by blocking the SGLT2 protein in the proximal convoluted tubule of the nephron, which reabsorbs about 90% of filtered glucose. This inhibition causes glycosuria and natriuresis, which lowers plasma glucose concentrations.
- 28. Glucagon-like peptide-1 (GLP-1) receptor agonists bind to and activate the GLP-1 receptor in a similar way to endogenous GLP-1. GLP-1 is a gut-derived hormone that regulates glucose homeostasis and is released after eating carbohydrates or fats. GLP-1 receptor agonists stimulate the pancreas to release insulin when needed, Slowing down digestion, inhibiting glucagon release after meals, reducing food intake, and delaying gastric emptying.
- 29. • Multi-functional peptide. • Manufactured by modifying the native GIP peptide sequence to bind to GIP and GLP-1 receptors. Tirzepatide • Mean half-life of about 5 days (116.7 hours), allowing for once-weekly dosing. • GIP receptor agonists promote the release of insulin in a glucose-dependent manner, meaning they enhance insulin secretion when blood glucose levels are high. • GLP-1 receptor agonists stimulate insulin secretion from pancreatic beta cells in response to elevated blood glucose levels. • GIP receptor agonists primarily enhance insulin secretion and may have other metabolic effects, while GLP-1 receptor agonists have broader effects including inhibiting glucagon secretion, delaying gastric emptying, and promoting satiety.
- 30. ● Amylin/GLP-1 dual receptor agonists - Cagrilintide ● GIP/glucagon/GLP-1 triple receptor agonists - Retatrutide ● Oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist - Orforglipron ● Once-weekly basal insulin analog - Insulin icodec NOVEL AGENTS THAT ARE IN DEVELOPMENT
- 31. Thank You!