Introduction of Cancer

part-I
Cancer
•2nd most common cause of death
•5-year survival rate is now 64% for those who are disease free,
or under treatment
•2030 - 20 million cancer cases annually worldwide

•Risk of developing cancer - depends on many factors

•Including age, lifestyle, Infectious agents, Genetic constitution
Basic facts about Cancer
➢ Cancer - a complex family of diseases

➢ That vary in their age of onset, rate of growth, state of cellular

differentiation, diagnostic detectability, invasiveness, metastatic
potential, response to treatment, and prognosis.

➢ Disease of abnormal gene expression via different mechanisms

➢ Imbalanced cell division and cell death

What causes Cancer?
Cancer can be induced in somatic cells
by:
➢ Carcinogens
➢ Tobacco – 12.5% cancers; - 20%
cancer deaths
➢ Alcohol – 1% cancers
➢ Radiation – Skin cancers
➢ Viruses/ Bacteria - 15%
➢ Heredity : 5 - 10%
➢ Injuries: Do not cause cancer
➢ Stress: Does not cause cancer
Incidence and facts:
➢ Cancer - leading cause of death in the Western world

➢ In the USA, leading cause of death after 1999 in young population

(< 85)

➢ Highest mortality – Breast, lung, colorectal and prostate cancers

➢ 10-20 years may pass before cancer manifests into clinically

detectable form
Cancer and its relation to age
• Cancer is usually disease of aging

• Average age at the time of diagnosis for cancer of all sites is 67 years

• 76% of all cancers are diagnosed at age 55 or older

• Relatively rare in children, but second leading cause of death in

children ages 1–14 – leukaemia most common cause of death
 Cancer cases in India

BMC Cancer volume 22, Article number: 527 (2022) 

➢ Major increase in deaths due to lung cancer.

➢ In addition, pollution, diet, and other lifestyle changes may have

contributed to increase in cancer mortality rates

➢ Stomach cancer mortality has dropped significantly since the early

1900s, presumably because of better methods of food preservation

➢ However, mortality rates have been same for breast, colon, and
prostate,
 Increase in Survival Rates
• More and more people are being cured of their cancers today

• In 1940s, only 1 in 4 persons diagnosed with cancer lived at least 5

years after treatment; in the 1990s it rose to 4 in 10.

• The relative 5-year survival rate is about 64% for all cancers taken
together
What is Cancer?
•Cancer is an abnormal growth of cells caused
by;
•Multiple changes in gene expression leading to
•Dysregulated balance of cell proliferation and cell
death
•Invade tissues and metastasize to distant sites that
leads to death
Defect in Cellular Proliferation
•Cancer cells are characterized by the loss of contact inhibition
grow on top of one another and on top of or between normal
cells

•Cancer cells respond differently than normal cells to

intracellular signals regulating equilibrium and divide
indiscriminately.
Defect in Cellular Proliferation
• Once mutated, the cell can;
➢ Die
➢ Recognize damage and
repair itself
➢ Survive and pass on the
damage

Surviving mutated cells have potential to become malignant

 Characteristics of Cancer Cells

When a malignant tumor no longer resembles the tissue of origin, it is

called anaplastic or undifferentiated.

➢ Self-sufficiency in growth signals

➢ Insensitivity to growth-inhibitory (antigrowth) signals
➢ Evasion of programmed cell death (apoptosis)
➢ Limitless replication potential
➢ Sustained angiogenesis
➢ Tissue invasion and metastasis
 Difference in Normal and Cancer cells
➢ Grow in the absence of signals telling them to grow.
Normal cells only grow when they receive such signals.

➢ Ignore signals that normally tell cells to stop dividing

or to die (a process known as programmed cell death,
or apoptosis).
➢Tell blood vessels to grow toward tumors. These blood
vessels supply tumors with oxygen and nutrients and remove
waste products from tumors.

➢Hide from the immune system. The immune system

normally eliminates damaged or abnormal cells.

➢Trick the immune system into helping cancer cells stay

➢ Accumulate multiple changes in their chromosomes, such as
duplications and deletions of chromosome parts. Some cancer cells
have double the normal number of chromosomes.

➢ Rely on different kinds of nutrients than normal cells. In

addition, some cancer cells make energy from nutrients in a different
way than most normal cells. This lets cancer cells grow more quickly.
Defect in Cellular Proliferation
• Proto-oncogenes:
➢ Normal cellular genes that are important regulators on normal
cellular processes
➢ Mutations that alter their expression can activate them to act as
oncogenes (tumor-inducing)

• Tumor suppressor genes:

• Suppress growth of tumours: Mutations render them inactive
Tumor suppressor Genes
 Tumors arise from many specialized cell types
throughout the body

•Majority of human tumors arise from epithelial tissues –

carcinomas

“The epithelium is a type of body tissue that forms the covering on

all internal and external surfaces of your body, lines body cavities
and hollow organs and is the major tissue in glands”
Epithelium Tissue
“The epithelium is a type of
body tissue that forms the
covering on all internal and
external surfaces of your body,
lines body cavities and hollow
organs, and is the major tissue
in glands”
The organs in body are composed of four basic types of tissue,
including:

➢ Epithelial.
➢ Connective.
➢ Muscular.
➢ Nervous.

All substances that enter or leave an organ must cross the epithelial
tissue first.
Different types of epithelial tissue throughout
body:
➢ The outer layer of your skin (epidermis)

➢ The lining of your intestines.

➢ The lining of your respiratory tract.

➢ The lining of your abdominal cavity.

➢ The sweat glands.

Epithelial tissue is made up of epithelial cells.

• The cells can be different shapes and can be arranged in a single

layer or multiple layers depending on where they are in your body
and what kind of functions they have.
 Types of epithelial cells based on shape
➢ Squamous epithelium: Squamous epithelial cells are flat and sheet-
like in appearance.

➢ Cuboidal epithelium: Cuboidal epithelial cells are cube-like in

appearance, meaning they have equal width, height and depth.

➢ Columnar epithelium: Columnar epithelial cells are column-like in

appearance, meaning they are taller than they are wide.
 Types of epithelial cells based on their
arrangement
• Simple: A simple epithelium means that there’s only one layer of cells.

• Stratified: A stratified epithelium is made up of more than one layer

of cells.

• Pseudostratified: A pseudostratified epithelium is made up of closely

packed cells that appear to be arranged in layers because they’re
different sizes, but there’s actually just one layer of cells.
Types of epithelial cells in your body
Epithelial cells based on specialized functions

➢ Transitional epithelium: Made up of several layers of cells that

become flattened when stretched. It lines most of urinary tract and
allows your bladder to expand.

➢ Glandular epithelium: This type of epithelium is specialized to

produce and secrete (release) substances. It’s found in glands, releas
hormones, protein and water

➢ Olfactory epithelium: The olfactory epithelium, located within

What does the epithelium do?
• Protection: Skin is made up of epithelial tissue
• Secretion: Epithelial tissue in your glands secrete enzyme, hormones
• Absorption: liver, lungs and intestine can allow the absorption of
certain substances
• Excretion: kidneys excrete waste
• Filtration: respiratory tract filters out dirt and particles
• Diffusion:
• Sensory reception: Sensory nerve endings that are embedded in
epithelial tissue allow body to receive outside sensory stimuli
Carcinomas arise from epithelial cells
What conditions affect epithelial tissue?

• Epithelial tissue is the potential for malignancy development as

adenocarcinoma or papillary thyroid carcinoma, which are two types
of cancer.

• Adenocarcinoma cancers affect the glandular epithelial tissue that lines

the organs and is the most common type of cancer affecting organs
 Adenocarcinoma is responsible for:
➢ Almost all prostate cancers.

➢ Most breast cancers.

➢ About 96% of colorectal cancers.

➢ Approximately 95% of pancreatic cancers.

➢ Around 40% of non-small cell lung cancers.

 Types of cancer
➢ Carcinoma. This type of cancer affects organs and glands, such as
the lungs, breasts, pancreas and skin. Carcinoma is the most common
type of cancer.

➢ Sarcoma. This cancer affects soft or connective tissues, such as

muscle, fat, bone, cartilage or blood vessels.

➢ Melanoma. Sometimes cancer can develop in the cells that pigment

your skin. These cancers are called melanoma.

➢ Lymphoma. This cancer affects your lymphocytes or white blood

• Arise from blood-forming cells

• Leukemia – cells of hematopoietic

lineage

• Lymphoma – cells of lymphoid lineage

(T or B cells) aggregate to form

• solid tumor masses, most frequently

found in lymph nodes
 Cancers develop progressively

Not every change in the body’s tissues is cancer.

Some tissue changes may develop into cancer if they are not treated
• Hyperplasia occurs when cells within a tissue multiply faster than

normal and extra cells build up.

• Dysplasia is a more advanced condition than hyperplasia. In dysplasia,

there is also a buildup of extra cells

• Carcinoma in situ is an even more advanced condition. Although it is

sometimes called stage 0 cancer, it is not cancer because the abnormal

cells do not invade nearby tissue the way that cancer cells do.
Development of Colorectal Carcinoma
Inherited and Familial Cancers
• In some relatively uncommon cancers there is
a strong hereditary factor

• e.g. familial polyposis coli –

• By transmission of an mutant inactive
Adenomatous polyposis coli (APC), the
children of an affected parent are likely to
develop the condition of multiple polyps in the
large bowel
➢ More common cancers with an increased familial incidence are
cancers of the breast, stomach and bowel

➢ BRCA1 BRCA2 mutations – breast cancer

➢ Stomach cancer – people with blood group A at higher risk

Tumor suppressor genes – both alleles need to be inactive for

malignant transformation
 Specific carcinogenic agents
Cancer Exposure
• Liver angiosarcoma Vinyl chloride
• Acute leukemias benzene
• Nasal adenocarcinoma hardwood dust
• Osteosarcoma radium
• Skin carcinoma Arsenic
• Mesothelioma Asbestos
 Causes of Cancer
• Only 5% cancers are hereditary
• Chemicals (e.g. from smoking), radiation, viruses, and heredity all
contribute to the development of cancer by triggering changes in a
cell's genes.
• Oncogenes – damaged genes, related to proto-oncogenes e.g. Ras
• Tumor suppressor genes – e.g. p53, pRb
• Mismatch repair genes -
• Telomerase gene -
Reasons behind the development of Cancer
➢ Causes - Chemical, environmental, genetic, immunologic,
viral, or spontaneous in origin

➢ Initiation: Mutation of genetic structure that has potential to

develop into clone of neoplastic cells
Process of cancer
development
 Promotion

•Characterized by the reversible proliferation of altered cells

•Activities of promotion (e.g. by obesity, smoking, alcohol) are

reversible

•Latent period : Initial genetic alteration to clinical evidence of

cancer
Progression

• Characterized by increased growth rate of tumor as well as its

invasiveness and metastasis

• Metastasis = spread of cancer from primary (initial) site to distant site

• Metastasis process begins with rapid growth of primary tumor;

Tumor angiogenesis - formation of blood vessels within the tumor;

critical for tumor survival
Invasion and Metastasis

• Invasion - direct migration

and penetration into
neighboring tissues

• Metastasis - cancer cells

penetrate into lymphatics and
blood vessels
Defect in Cellular Proliferation

➢ Pyramid Effect: Cancer are clonal

in origin

➢ Each cell division creates two or

more offspring cells

➢ Continuous tumor growth

Genetic and non-genetic clonal diversity in cancer
evolution

Nature Reviews Cancer volume 21, pages379–392 (2021)

 Role of Immune System
•Immune response is to reject or destroy cancer cells if
perceived as non-self

•Some cancer cells have changes on their surface antigens

• Tumor-associated antigens (TAAs): Response to TAAs is termed

immunologic surveillance
• Lymphocytes continually check cell surfaces and detect and destroy
cells with abnormalities

Cancer cells evade immune system because of

• Suppression of factors that stimulate T cells
• Weak surface antigens allow cancer cells to “sneak through”
surveillance
How Cancers Evade Immune System?
• Development of tolerance of immune system

• Suppression of immune response to products secreted by cancer cells

• Induction of suppressor T cells

• Blocking antibodies that bind TAAs

Diagnosis of Cancer
• Biopsy involves histologic examination by a pathologist of a piece of
tissue;

• Needle
• Incisional
• Excisional
 Histologic Grade of Malignancy

• Based on degree of differentiation of a cancer

• Mostly, less differentiated tumors are more aggressive

• Grade I (75% to 100% differentiation), Grade II (50% to 75%), Grade

III (25% to 50%), and Grade IV (0% to 25%)

 Tumor Staging

Objectives of the classification system

• To aid oncologists in planning treatment;

• To provide categories for estimating prognosis and evaluating

results of treatment; and

• To facilitate exchange of information

 Classification of Cancer

• TNM Classification;

• Tumor size
• Spread to lymph nodes
• Metastasis
 Criteria for lymph node involvement (N)
• N1 - palpable small (2-3 cm diameter) lymph nodes with tumor
involvement,
Mobile

• N2 - firm, hard, partially movable nodes (3 to 5 cm), partially invasive, and

they
may feel as if they were matted together;

• N3 - large lymph nodes (> 5 cm) with complete fixation and invasion into
adjacent
Tissues
 Seven Warning Signs of Cancer
• Change in bowel or bladder habits
• A sore throat that does not heal
• Unusual bleeding or discharge from body orifice
• Thickening or lump in breast or elsewhere
• Indigestion or difficulty in swallowing
• Obvious change in wart or mole
• Nagging cough or hoarseness
 Cancer Prevention and Detection

•Reduce or avoid exposure to known or suspected carcinogens

•Eat balanced diet
•Exercise regularly
•Adequate rest
•Health examination on a regular basis
 Cancer Prevention and Detection
• Eliminate, reduce, or change perceptions of stressors and enhance
ability to cope
• Enjoy consistent periods of relaxation and leisure
• Know 7 warning signs of cancer
• Self-examination
• Seek medical care if cancer is suspected
Reference Book:

• Cancer Biology 4th ed. - R. Ruddon (Oxford, 2007)

• Introduction to Cancer Biology – Momna Hejmadi (2010)