CANCER

INTRODUCTION
Cancer is a group of diseases involving abnormal cell growth with the
potential to invade or spread to other parts of the body. These contrast with benign
tumors, which do not spread. Possible signs and symptoms include a lump,
abnormal bleeding, prolonged cough, unexplained weight loss, and a change
in bowel movements. While these symptoms may indicate cancer, they can also
have other causes. Over 100 types of cancers affect humans.
Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due
to obesity, poor diet, lack of physical activity or excessive alcohol
consumption. Other factors include certain infections, exposure to ionizing radiation,
and environmental pollutants. Infection with specific viruses, bacteria and parasites
is an environmental factor causing approximately 16-18% of cancers
worldwide. These infectious agents include Helicobacter pylori, hepatitis B, hepatitis
C, human papillomavirus infection, Epstein–Barr virus, Human T-lymphotropic virus
1, Kaposi's sarcoma-associated herpesvirus and Merkel cell polyomavirus. Human
immunodeficiency virus (HIV) does not directly cause cancer but it causes immune
deficiency that can magnify the risk due to other infections, sometimes up to several
thousand fold (in the case of Kaposi's sarcoma). Importantly, vaccination
against hepatitis B and human papillomavirus have been shown to nearly eliminate
risk of cancers caused by these viruses in persons successfully vaccinated prior to
infection.
These environmental factors act, at least partly, by changing the genes of a
cell. Typically, many genetic changes are required before cancer
develops. Approximately 5–10% of cancers are due to inherited genetic
defects. Cancer can be detected by certain signs and symptoms or screening
tests. It is then typically further investigated by medical imaging and confirmed
by biopsy.
The risk of developing certain cancers can be reduced by not smoking, maintaining a
healthy weight, limiting alcohol intake, eating plenty of vegetables, fruits, and whole
grains, vaccination against certain infectious diseases, limiting consumption
of processed meat and red meat, and limiting exposure to direct sunlight. Early
detection through screening is useful for cervical and colorectal cancer. The benefits
of screening for breast cancer are controversial. Cancer is often treated with some
combination of radiation therapy, surgery, chemotherapy and targeted therapy. Pain
and symptom management are an important part of care. Palliative care is
particularly important in people with advanced disease. The chance of survival
depends on the type of cancer and extent of disease at the start of treatment. In
children under 15 at diagnosis, the five-year survival rate in the developed world is
on average 80%. For cancer in the United States, the average five-year survival rate
is 66% for all ages.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 1

 CANCER

In 2015, about 90.5 million people worldwide had cancer. In 2019, annual cancer
cases grew by 23.6 million people, and there were 10 million deaths worldwide,
representing over the previous decade increases of 26% and 21%, respectively.
The most common types of cancer in males are lung cancer, prostate
cancer, colorectal cancer, and stomach cancer. In females, the most common types
are breast cancer, colorectal cancer, lung cancer, and cervical cancer. If skin
cancer other than melanoma were included in total new cancer cases each year, it
would account for around 40% of cases. In children, acute lymphoblastic
leukemia and brain tumors are most common, except in Africa, where non-Hodgkin
lymphoma occurs more often. In 2012, about 165,000 children under 15 years of age
were diagnosed with cancer. The risk of cancer increases significantly with age, and
many cancers occur more commonly in developed countries. Rates are increasing
as more people live to an old age and as lifestyle changes occur in the developing
world. The global total economic costs of cancer were estimated at US$1.16 trillion
(equivalent to $1.62 trillion in 2023) per year as of 2010.

Etymology and definitions

The word comes from the ancient Greek καρκίνος, meaning 'crab' and 'tumor'. Greek
physicians Hippocrates and Galen, among others, noted the similarity of crabs to
some tumors with swollen veins. The word was introduced in English in the modern
medical sense around 1600.
Cancers comprise a large family of diseases that involve abnormal cell growth with
the potential to invade or spread to other parts of the body. They form a subset
of neoplasms. A neoplasm or tumor is a group of cells that have undergone
unregulated growth and will often form a mass or lump, but may be distributed
diffusely.
All tumor cells show the six hallmarks of cancer. These characteristics are required
to produce a malignant tumor. They include:

 Cell growth and division absent the proper signals

 Continuous growth and division even given contrary signals
 Avoidance of programmed cell death
 Limitless number of cell divisions
 Promoting blood vessel construction
 Invasion of tissue and formation of metastases
The progression from normal cells to cells that can form a detectable mass to cancer
involves multiple steps known as malignant progression.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 2

 CANCER

Classification
Further information: List of cancer types and List of oncology-related terms

(Figure -1)
A large proportion of cancers are adenocarcinomas, with typical histopathology
features shown, although they vary substantially from case to case.
Cancers are classified by the type of cell that the tumor cells resemble and is
therefore presumed to be the origin of the tumor. These types include:

 Carcinoma: Cancers derived from epithelial cells. This group includes many of
the most common cancers and include nearly all those in
the breast, prostate, lung, pancreas and colon. Most of these are of
the adenocarcinoma type, which means that the cancer has gland-like
differentiation.
 Sarcoma: Cancers arising from connective tissue (i.e. bone, cartilage, fat, nerve),
each of which develops from cells originating in mesenchymal cells outside
the bone marrow.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 3

 CANCER

 Lymphoma and leukemia: These two classes arise from hematopoietic (blood-
forming) cells that leave the marrow and tend to mature in the lymph nodes and
blood, respectively.
 Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in
the testicle or the ovary (seminoma and dysgerminoma, respectively).
 Blastoma: Cancers derived from immature "precursor" cells or embryonic tissue.
Cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix,
with the Latin or Greek word for the organ or tissue of origin as the root. For
example, cancers of the liver parenchyma arising from malignant epithelial cells is
called hepatocarcinoma, while a malignancy arising from primitive liver precursor
cells is called a hepatoblastoma and a cancer arising from fat cells is called
a liposarcoma. For some common cancers, the English organ name is used. For
example, the most common type of breast cancer is called ductal carcinoma of the
breast. Here, the adjective ductal refers to the appearance of cancer under the
microscope, which suggests that it has originated in the milk ducts.
Benign tumors (which are not cancers) are named using -oma as a suffix with the
organ name as the root. For example, a benign tumor of smooth muscle cells is
called a leiomyoma (the common name of this frequently occurring benign tumor in
the uterus is fibroid). Confusingly, some types of cancer use the -noma suffix,
examples including melanoma and seminoma.
Some types of cancer are named for the size and shape of the cells under a
microscope, such as giant cell carcinoma, spindle cell carcinoma and small-cell
carcinoma.

Signs and symptoms

Symptoms of cancer metastasis depend on the location of the tumor.
When cancer begins, it produces no symptoms. Signs and symptoms appear as the
mass grows or ulcerates. The findings that result depend on cancer's type and
location. Few symptoms are specific. Many frequently occur in individuals who have
other conditions. Cancer can be difficult to diagnose and can be considered a "great
imitator".
People may become anxious or depressed post-diagnosis. The risk of suicide in
people with cancer is approximately double.
Local symptoms
Local symptoms may occur due to the mass of the tumor or its ulceration. For
example, mass effects from lung cancer can block the bronchus resulting in cough
or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it
difficult or painful to swallow; and colorectal cancer may lead to narrowing or
blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 4

 CANCER

produce observable lumps. Ulceration can cause bleeding that can lead to
symptoms such as coughing up blood (lung cancer), anemia or rectal
bleeding (colon cancer), blood in the urine (bladder cancer), or abnormal vaginal
bleeding (endometrial or cervical cancer). Although localized pain may occur in
advanced cancer, the initial tumor is usually painless. Some cancers can cause a
buildup of fluid within the chest or abdomen.
Systemic symptoms
Systemic symptoms may occur due to the body's response to the cancer. This may
include fatigue, unintentional weight loss, or skin changes. Some cancers can
[34]

cause a systemic inflammatory state that leads to ongoing muscle loss and
weakness, known as cachexia.
Some cancers, such as Hodgkin's disease, leukemias, and liver or kidney cancers,
can cause a persistent fever.
Shortness of breath, called dyspnea, is a common symptom of cancer and its
treatment. The causes of cancer-related dyspnea can include tumors in or around
the lung, blocked airways, fluid in the lungs, pneumonia, or treatment reactions
including an allergic response. Treatment for dyspnea in patients with advanced
cancer can include fans, bilevel ventilation, acupressure / reflexology and
multicomponent nonpharmacological interventions.
Some systemic symptoms of cancer are caused by hormones or other molecules
produced by the tumor, known as paraneoplastic syndromes. Common
paraneoplastic syndromes include hypercalcemia, which can cause altered mental
state, constipation and dehydration, or hyponatremia, which can also cause altered
mental status, vomiting, headaches, or seizures.
Metastasis
Metastasis is the spread of cancer to other locations in the body. The dispersed
tumors are called metastatic tumors, while the original is called the primary tumor.
Almost all cancers can metastasize. Most cancer deaths are due to cancer that has
[39]

metastasized.[40]

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 5

 CANCER

(Figure -2)
Metastasis is common in the late stages of cancer and it can occur via the blood or
the lymphatic system or both. The typical steps in metastasis are
local invasion, intravasation into the blood or lymph, circulation through the
body, extravasation into the new tissue, proliferation and angiogenesis. Different
types of cancers tend to metastasize to particular organs, but overall the most
common places for metastases to occur are the lungs, liver, brain, and the bones. [39]

While some cancers can be cured if detected early, metastatic cancer is more
difficult to treat and control. Nevertheless, some recent treatments are demonstrating
encouraging results.[41]

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 6

 CANCER

Causes

The GHS Hazard pictogram for carcinogenic

substancesShare of cancer deaths attributed to tobacco in 2016.
The majority of cancers, some 90–95% of cases, are due to genetic mutations from
environmental and lifestyle factors. The remaining 5–10% are due to inherited
genetics. Environmental refers to any cause that is not inherited, such as lifestyle,
economic, and behavioral factors and not merely pollution. Common environmental
factors that contribute to cancer death include tobacco use (25–30%), diet
and obesity (30–35%), infections (15–20%), radiation (both ionizing and non-
ionizing, up to 10%), lack of physical activity, and pollution. Psychological stress
does not appear to be a risk factor for the onset of cancer, though it may worsen
outcomes in those who already have cancer.
Environmental or lifestyle factors that caused cancer to develop in an individual can
be identified by analyzing mutational signatures from genomic sequencing of tumor
DNA. For example, this can reveal if lung cancer was caused by tobacco smoke, if
skin cancer was caused by UV radiation, or if secondary cancers were caused by
previous chemotherapy treatment.
Cancer is generally not a transmissible disease. Exceptions include rare
transmissions that occur with pregnancies and occasional organ donors. However,
transmissible infectious diseases such as hepatitis B, Epstein-Barr virus, Human
Papilloma Virus and HIV, can contribute to the development of cancer.
Chemicals
Further information: Alcohol and cancer and Smoking and cancer

(Figure -3)

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 7

 CANCER

The incidence of lung cancer is highly correlated with smoking.

Exposure to particular substances have been linked to specific types of cancer.
These substances are called carcinogens.
Tobacco smoke, for example, causes 90% of lung cancer. Tobacco use can cause
cancer throughout the body including in the mouth and throat, larynx, esophagus,
stomach, bladder, kidney, cervix, colon/rectum, liver and pancreas. Tobacco smoke
contains over fifty known carcinogens, including nitrosamines and polycyclic
aromatic hydrocarbons.
Tobacco is responsible for about one in five cancer deaths worldwide and about one
in three in the developed world. Lung cancer death rates in the United States have
mirrored smoking patterns, with increases in smoking followed by dramatic increases
in lung cancer death rates and, more recently, decreases in smoking rates since the
1950s followed by decreases in lung cancer death rates in men since 1990.
In Western Europe, 10% of cancers in males and 3% of cancers in females are
attributed to alcohol exposure, especially liver and digestive tract cancers. Cancer
from work-related substance exposures may cause between 2 and 20% of
cases, causing at least 200,000 deaths. Cancers such as lung cancer
and mesothelioma can come from inhaling tobacco smoke or asbestos fibers,
or leukemia from exposure to benzene.
Exposure to perfluorooctanoic acid (PFOA), which is predominantly used in the
production of Teflon, is known to cause two kinds of cancer.
Chemotherapy drugs such as platinum-based compounds are carcinogens that
increase the risk of secondary cancers
Azathioprine, an immunosuppressive medication, is a carcinogen that can
cause primary tumors to develop.
Diet and exercise
Diet, physical inactivity, and obesity are related to up to 30–35% of cancer deaths. In
the United States, excess body weight is associated with the development of many
types of cancer and is a factor in 14–20% of cancer deaths. A UK study including
data on over 5 million people showed higher body mass index to be related to at
least 10 types of cancer and responsible for around 12,000 cases each year in that
country. Physical inactivity is believed to contribute to cancer risk, not only through
its effect on body weight but also through negative effects on the immune
system and endocrine system. More than half of the effect from the diet is due
to overnutrition (eating too much), rather than from eating too few vegetables or
other healthful foods.
Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric
cancer. Aflatoxin B1, a frequent food contaminant, causes liver cancer. Betel
nut chewing can cause oral cancer. National differences in dietary practices may

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 8

 CANCER

partly explain differences in cancer incidence. For example, gastric cancer is more
common in Japan due to its high-salt diet while colon cancer is more common in the
United States. Immigrant cancer profiles mirror those of their new country, often
within one generation.
Infection
Worldwide, approximately 18% of cancer deaths are related to infectious
diseases. This proportion ranges from a high of 25% in Africa to less than 10% in the
developed world. Viruses are the usual infectious agents that cause cancer
but bacteria and parasites may also play a role. Oncoviruses (viruses that can cause
human cancer) include:

 Human papillomavirus (cervical cancer),

 Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal
carcinoma),
 Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion
lymphomas),
 Hepatitis B and hepatitis C viruses (hepatocellular carcinoma)
 Human T-cell leukemia virus-1 (T-cell leukemias).
 Merkel cell polyomavirus (Merkel cell carcinoma)
Bacterial infection may also increase the risk of cancer, as seen in

 Helicobacter pylori-induced gastric carcinoma.

 Colibactin, a genotoxin associated with Escherichia coli infection (colorectal
cancer)
Parasitic infections associated with cancer include:

 Schistosoma haematobium (squamous cell carcinoma of the bladder)

 The liver flukes, Opisthorchis viverrini and Clonorchis sinensis
(cholangiocarcinoma).
Radiation
Radiation exposure such as ultraviolet radiation and radioactive material is a risk
factor for cancer. Many non-melanoma skin cancers are due to ultraviolet radiation,
mostly from sunlight. Sources of ionizing radiation include medical imaging
and radon gas.
Ionizing radiation is not a particularly strong mutagen. Residential exposure
to radon gas, for example, has similar cancer risks as passive smoking. Radiation is
a more potent source of cancer when combined with other cancer-causing agents,
such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the
body, in all animals and at any age. Children are twice as likely to develop radiation-
induced leukemia as adults; radiation exposure before birth has ten times the effect.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 9

 CANCER

Medical use of ionizing radiation is a small but growing source of radiation-induced

cancers. Ionizing radiation may be used to treat other cancers, but this may, in some
cases, induce a second form of cancer. It is also used in some kinds of medical
imaging.
Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and
other skin malignancies. Clear evidence establishes ultraviolet radiation, especially
the non-ionizing medium wave UVB, as the cause of most non-melanoma skin
cancers, which are the most common forms of cancer in the world.
Non-ionizing radio frequency radiation from mobile phones, electric power
transmission and other similar sources has been described as a possible
carcinogen by the World Health Organization's International Agency for Research on
Cancer. Evidence, however, has not supported a concern. This includes that studies
have not found a consistent link between mobile phone radiation and cancer risk.
Heredity
The vast majority of cancers are non-hereditary (sporadic). Hereditary cancers are
primarily caused by an inherited genetic defect. Less than 0.3% of the population are
carriers of a genetic mutation that has a large effect on cancer risk and these cause
less than 3–10% of cancer. Some of these syndromes include: certain inherited
mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast
cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC
or Lynch syndrome), which is present in about 3% of people with colorectal
cancer, among others.
Statistically for cancers causing most mortality, the relative risk of developing
colorectal cancer when a first-degree relative (parent, sibling or child) has been
diagnosed with it is about 2. The corresponding relative risk is 1.5 for lung
cancer, and 1.9 for prostate cancer. For breast cancer, the relative risk is 1.8 with a
first-degree relative having developed it at 50 years of age or older, and 3.3 when
the relative developed it when being younger than 50 years of age.
Taller people have an increased risk of cancer because they have more cells than
shorter people. Since height is genetically determined to a large extent, taller people
have a heritable increase of cancer risk.
Physical agents
Some substances cause cancer primarily through their physical, rather than
chemical, effects. A prominent example of this is prolonged exposure to asbestos,
naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of
the serous membrane) usually the serous membrane surrounding the lungs. Other
substances in this category, including both naturally occurring and synthetic
asbestos-like fibers, such as wollastonite, attapulgite, glass wool and rock wool, are
believed to have similar effects. Non-fibrous particulate materials that cause cancer
include powdered metallic cobalt and nickel and crystalline silica (quartz, cristobalite

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 10

 CANCER

and tridymite). Usually, physical carcinogens must get inside the body (such as
through inhalation) and require years of exposure to produce cancer.
Physical trauma resulting in cancer is relatively rare. Claims that breaking bones
resulted in bone cancer, for example, have not been proven. Similarly, physical
trauma is not accepted as a cause for cervical cancer, breast cancer or brain
cancer. One accepted source is frequent, long-term application of hot objects to the
body. It is possible that repeated burns on the same part of the body, such as those
produced by kanger and kairo heaters (charcoal hand warmers), may produce skin
cancer, especially if carcinogenic chemicals are also present. Frequent consumption
of scalding hot tea may produce esophageal cancer. Generally, it is believed that
cancer arises, or a pre-existing cancer is encouraged, during the process of healing,
rather than directly by the trauma. However, repeated injuries to the same tissues
might promote excessive cell proliferation, which could then increase the odds of a
cancerous mutation.
Chronic inflammation has been hypothesized to directly cause mutation.
Inflammation can contribute to proliferation, survival, angiogenesis and migration of
cancer cells by influencing the tumor microenvironment. Oncogenes build up an
inflammatory pro-tumorigenic microenvironment.
Hormones
Hormones also play a role in the development of cancer by promoting cell
proliferation. Insulin-like growth factors and their binding proteins play a key role in
cancer cell proliferation, differentiation and apoptosis, suggesting possible
involvement in carcinogenesis.
Hormones are important agents in sex-related cancers, such as cancer of the
breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone
cancer. For example, the daughters of women who have breast cancer have
significantly higher levels of estrogen and progesterone than the daughters of
women without breast cancer. These higher hormone levels may explain their higher
risk of breast cancer, even in the absence of a breast-cancer gene. Similarly, men of
African ancestry have significantly higher levels of testosterone than men of
European ancestry and have a correspondingly higher level of prostate cancer. Men
of Asian ancestry, with the lowest levels of testosterone-activating androstanediol
glucuronide, have the lowest levels of prostate cancer.
Other factors are relevant: obese people have higher levels of some hormones
associated with cancer and a higher rate of those cancers. Women who
take hormone replacement therapy have a higher risk of developing cancers
associated with those hormones. On the other hand, people who exercise far more
than average have lower levels of these hormones and lower risk of
cancer. Osteosarcoma may be promoted by growth hormones. Some treatments and
prevention approaches leverage this cause by artificially reducing hormone levels
and thus discouraging hormone-sensitive cancers.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 11

 CANCER

Autoimmune diseases
There is an association between celiac disease and an increased risk of all cancers.
People with untreated celiac disease have a higher risk, but this risk decreases with
time after diagnosis and strict treatment. This may be due to the adoption of
a gluten-free diet, which seems to have a protective role against development of
malignancy in people with celiac disease. However, the delay in diagnosis and
initiation of a gluten-free diet seems to increase the risk of malignancies. Rates of
gastrointestinal cancers are increased in people with Crohn's disease and ulcerative
colitis, due to chronic inflammation. Immunomodulators and biologic agents used to
treat these diseases may promote developing extra-intestinal malignancies.

Pathophysiology
Main article: Carcinogenesis

Genetics

Cancers are caused by a series of mutations. Each mutation alters the behavior of
the cell somewhat.
Cancer is fundamentally a disease of tissue growth regulation. For a normal cell
to transform into a cancer cell, the genes that regulate cell growth and differentiation
must be altered.
The affected genes are divided into two broad categories. Oncogenes are genes that
promote cell growth and reproduction. Tumor suppressor genes are genes that
inhibit cell division and survival. Malignant transformation can occur through the
formation of novel oncogenes, the inappropriate over-expression of normal
oncogenes, or by the under-expression or disabling of tumor suppressor genes.
Typically, changes in multiple genes are required to transform a normal cell into a
cancer cell.
Genetic changes can occur at different levels and by different mechanisms. The gain
or loss of an entire chromosome can occur through errors in mitosis. More common
are mutations, which are changes in the nucleotide sequence of genomic DNA.
Large-scale mutations involve the deletion or gain of a portion of a chromosome.
Genomic amplification occurs when a cell gains copies (often 20 or more) of a small
chromosomal locus, usually containing one or more oncogenes and adjacent genetic
material. Translocation occurs when two separate chromosomal regions become
abnormally fused, often at a characteristic location. A well-known example of this is
the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which
occurs in chronic myelogenous leukemia and results in production of the BCR-
abl fusion protein, an oncogenic tyrosine kinase.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 12

 CANCER

Small-scale mutations include point mutations, deletions, and insertions, which may
occur in the promoter region of a gene and affect its expression, or may occur in the
gene's coding sequence and alter the function or stability of its protein product.
Disruption of a single gene may also result from integration of genomic material from
a DNA virus or retrovirus, leading to the expression of viral oncogenes in the affected
cell and its descendants.
Replication of the data contained within the DNA of living cells will probabilistically
result in some errors (mutations). Complex error correction and prevention are built
into the process and safeguard the cell against cancer. If a significant error occurs,
the damaged cell can self-destruct through programmed cell death, termed
apoptosis. If the error control processes fail, then the mutations will survive and be
passed along to daughter cells.
Some environments make errors more likely to arise and propagate. Such
environments can include the presence of disruptive substances called carcinogens,
repeated physical injury, heat, ionising radiation, or hypoxia.
The errors that cause cancer are self-amplifying and compounding, for example:

 A mutation in the error-correcting machinery of a cell might cause that cell and its
children to accumulate errors more rapidly.
 A further mutation in an oncogene might cause the cell to reproduce more rapidly
and more frequently than its normal counterparts.
 A further mutation may cause loss of a tumor suppressor gene, disrupting the
apoptosis signaling pathway and immortalizing the cell.
 A further mutation in the signaling machinery of the cell might send error-causing
signals to nearby cells.
The transformation of a normal cell into cancer is akin to a chain reaction caused by
initial errors, which compound into more severe errors, each progressively allowing
the cell to escape more controls that limit normal tissue growth. This rebellion-like
scenario is an undesirable survival of the fittest, where the driving forces
of evolution work against the body's design and enforcement of order. Once cancer
has begun to develop, this ongoing process, termed clonal evolution, drives
progression towards more invasive stages. Clonal evolution leads to intra-tumour
heterogeneity (cancer cells with heterogeneous mutations) that complicates
designing effective treatment strategies and requires an evolutionary approach to
designing treatment.
Characteristic abilities developed by cancers are divided into categories, specifically
evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth
signals, sustained angiogenesis, limitless replicative potential, metastasis,
reprogramming of energy metabolism and evasion of immune destruction.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 13

 CANCER

(Figure -4)

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 14

 CANCER

Eoigenetics

The central role of DNA damage and epigenetic defects in DNA repair genes in
carcinogenesis
The classical view of cancer is a set of diseases driven by progressive
genetic abnormalities that include mutations in tumor-suppressor genes and
oncogenes, and in chromosomal abnormalities. A role for epigenetic alterations was
identified in the early 21st century.
Epigenetic alterations are functionally relevant modifications to the genome that do
not change the nucleotide sequence. Examples of such modifications are changes
in DNA methylation (hypermethylation and hypomethylation), histone modification
and changes in chromosomal architecture (caused by inappropriate expression of
proteins such as HMGA2 or HMGA1). Each of these alterations regulates gene
expression without altering the underlying DNA sequence. These changes may
remain through cell divisions, endure for multiple generations, and can be
considered as equivalent to mutations.
Epigenetic alterations occur frequently in cancers. As an example, one study listed
protein coding genes that were frequently altered in their methylation in association
with colon cancer. These included 147 hypermethylated and 27 hypomethylated
genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon
cancers and many others were hypermethylated in more than 50% of colon cancers.
While epigenetic alterations are found in cancers, the epigenetic alterations in DNA
repair genes, causing reduced expression of DNA repair proteins, may be of
particular importance. Such alterations may occur early in progression to cancer and
are a possible cause of the genetic instability characteristic of cancers.
Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the
figure at the 4th level from the top. (In the figure, red wording indicates the central
role of DNA damage and defects in DNA repair in progression to cancer.) When
DNA repair is deficient DNA damage remains in cells at a higher than usual level
(5th level) and causes increased frequencies of mutation and/or epimutation (6th
level). Mutation rates increase substantially in cells defective in DNA mismatch repair
or in homologous recombinational repair (HRR). Chromosomal rearrangements and
aneuploidy also increase in HRR defective cells.
Higher levels of DNA damage cause increased mutation (right side of figure) and
increased epimutation. During repair of DNA double strand breaks, or repair of other
DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing.
Deficient expression of DNA repair proteins due to an inherited mutation can
increase cancer risks. Individuals with an inherited impairment in any of 34 DNA
repair genes (see article DNA repair-deficiency disorder) have increased cancer risk,
with some defects ensuring a 100% lifetime chance of cancer (e.g. p53

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 15

 CANCER

mutations). Germ line DNA repair mutations are noted on the figure's left side.
However, such germline mutations (which cause highly penetrant cancer
syndromes) are the cause of only about 1 percent of cancers.
In sporadic cancers, deficiencies in DNA repair are occasionally caused by a
mutation in a DNA repair gene but are much more frequently caused by epigenetic
alterations that reduce or silence expression of DNA repair genes. This is indicated
in the figure at the 3rd level. Many studies of heavy metal-induced carcinogenesis
show that such heavy metals cause a reduction in expression of DNA repair
enzymes, some through epigenetic mechanisms. DNA repair inhibition is proposed
to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition,
frequent epigenetic alterations of the DNA sequences code for small RNAs
called microRNAs (or miRNAs). miRNAs do not code for proteins, but can "target"
protein-coding genes and reduce their expression.
Cancers usually arise from an assemblage of mutations and epimutations that confer
a selective advantage leading to clonal expansion (see Field defects in progression
to cancer). Mutations, however, may not be as frequent in cancers as epigenetic
alterations. An average cancer of the breast or colon can have about 60 to 70
protein-altering mutations, of which about three or four may be "driver" mutations and
the remaining ones may be "passenger" mutations.
Metastasis
Metastasis is the spread of cancer to other locations in the body. The dispersed
tumors are called metastatic tumors, while the original is called the primary tumor.
Almost all cancers can metastasize. Most cancer deaths are due to cancer that has
metastasized.
Metastasis is common in the late stages of cancer and it can occur via the blood or
the lymphatic system or both. The typical steps in metastasis are local invasion,
intravasation into the blood or lymph, circulation through the body, extravasation into
the new tissue, proliferation and angiogenesis. Different types of cancers tend to
metastasize to particular organs, but overall the most common places for metastases
to occur are the lungs, liver, brain and the bones.
Metabolism
Normal cells typically generate only about 30% of energy from glycolysis, whereas
most cancers rely on glycolysis for energy production (Warburg effect). But a
minority of cancer types rely on oxidative phosphorylation as the primary energy
source, including lymphoma, leukemia, and endometrial cancer. Even in these
cases, however, the use of glycolysis as an energy source rarely exceeds 60%. A
few cancers use glutamine as the major energy source, partly because it provides
nitrogen required for nucleotide (DNA, RNA) synthesis. Cancer stem cells often use
oxidative phosphorylation or glutamine as a primary energy source.

Diagnosis
BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 16
 CANCER

(Figure -5)

Chest X-ray showing lung cancer in the left lung

Most cancers are initially recognized either because of the appearance of signs or
symptoms or through screening. Neither of these leads to a definitive diagnosis,
which requires the examination of a tissue sample by a pathologist. People with
suspected cancer are investigated with medical tests. These commonly
include blood tests, X-rays, (contrast) CT scans and endoscopy.
The tissue diagnosis from the biopsy indicates the type of cell that is proliferating,
its histological grade, genetic abnormalities and other features. Together, this
information is useful to evaluate the prognosis and to choose the best treatment.
Cytogenetics and immunohistochemistry are other types of tissue tests. These tests
provide information about molecular changes (such as mutations, fusion genes and
numerical chromosome changes) and may thus also indicate the prognosis and best
treatment.
Cancer diagnosis can cause psychological distress and psychosocial interventions,
such as talking therapy, may help people with this. Some people choose to
[124]

disclose the diagnosis widely; others prefer to keep the information private,
especially shortly after the diagnosis, or to disclose it only partially or to selected
people.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 17

 CANCER

CONCLUSION
A plan for the diagnosis and treatment of cancer is a key component of any
overall cancer control plan. Its main goal is to cure cancer patients or prolong their
life considerably, ensuring a good quality of life. In order for a diagnosis and
treatment programme to be effective, it must never be developed in isolation. It
needs to be linked to an early detection programme so that cases are detected at an
early stage, when treatment is more effective and there is a greater chance of cure.
It also needs to be integrated with a palliative care programme, so that patients with
advanced cancers, who can no longer benefit from treatment, will get adequate relief
from their physical, psychosocial and spiritual suffering. Furthermore, programmes
should include a awareness-raising component, to educate patients, family and
community members about the cancer risk factors and the need for taking preventive
measures to avoid developing cancer.

Where resources are limited, diagnosis and treatment services should initially target
all patients presenting with curable cancers, such as breast, cervical and oral
cancers that can be detected early. They could also include childhood acute
lymphatic leukaemia, which has a high potential for cure although it cannot be
detected early. Above all, services need to be provided in an equitable and
sustainable manner. As and when more resources become available, the
programme can be extended to include other curable cancers as well as cancers for
which treatment can prolong survival considerably.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 18

 CANCER

References
1. Signs and symptoms". NHS Choices.
2. World Health Organization.
3. Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B,
Aggarwal BB (September 2008). "Cancer is a preventable disease that requires major
lifestyle changes". Pharmaceutical Research.
4. "Targeted Cancer Therapies". cancer.gov. National Cancer Institute.
5. "SEER Stat Fact Sheets: All Cancer Sites". National Cancer Institute. Archived from the
original on 26 September 2010.
6. 444. doi:10.1001/jamaoncol.2021.6987. PMC 8719276. PMID 34967848.
7. "Defining Cancer". National Cancer Institute. 17 September 2007. Retrieved 28 March 2018.
8. "Obesity and Cancer Risk". National Cancer Institute. 3 January 2012.
9. Jayasekara H, MacInnis RJ, Room R, English DR (May 2016). "Long-Term Alcohol
Consumption and Breast, Upper Aero-Digestive Tract and Colorectal Cancer Risk: A
Systematic Review and Meta-Analysis". Alcohol and Alcoholism.
10. "Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis -
The Lancet Global Health".
11. World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 1.1. ISBN 978-92-
832-0429-9.
12. "Heredity and Cancer". American Cancer Society.
13. "How is cancer diagnosed?". American Cancer Society. 29 January 2013.
14. Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, Gapstur
S, Patel AV, Andrews K, Gansler T (2012). "American Cancer Society Guidelines on nutrition
and physical activity for cancer prevention: reducing the risk of cancer with healthy food
choices and physical activity". CA: A Cancer Journal for Clinicians.
15. Parkin DM, Boyd L, Walker LC (December 2011). "16. The fraction of cancer attributable to
lifestyle and environmental factors in the UK in 2010". British Journal of Cancer.
16. World Cancer Report 2014. World Health Organization. 2014.

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 19

 CANCER

INDEX

S.No. Particulars Page No.

1 Introduction of Cancer 1-2

2 Etymology and definitions 2-2

3 Classification 3-4

4 Signs and symptoms 4-4

5 Metastasis 5-6

6 Causes 6-6

7 Chemicals 7-8

8 Diet and exercise 8-11

9 Path physiology 12-13

10 Eoigenetics 14-15

11 Diagnosis 16-16

12 Conclusion 17-17

13 References 18-18

BHAGYODAY TIRTH PHARMACY COLLEGE SAGAR (M.P.) Page 20