Introducti

on to
Cancer
Biology
By, Dr. Huma Jawed
Ph.D., Pharmacology
• Cancer Biology provide a
foundation in the cell and
molecular biology of cancer
• In order to understand the process of carcinogenesis,
whereby a normal cell is transformed into a cancer cell,
we must know the workings of cell function and the
molecular pathways that underlie it.

• Translation of the knowledge of molecular pathways into

clinically important therapies.

Knowledge of the
molecular details in
important cellular and
biochemical pathways
can be applied to a new
trend of cancer
 Cancer
• Cancer is a group of diseases characterized by unregulated cell
growth and the invasion and spread of cells from the site of
origin, or primary site, to other sites in the body.
• Normally, human cells grow and multiply to form new cells as the
body needs them.

• Sometimes this orderly process breaks down, and abnormal or

damaged cells grow and multiply.

• These cells may form tumors, which are lumps of tissue. Tumors
can be cancerous or not cancerous (benign).

• Cancerous tumors spread into, or invade, nearby tissues and can

travel to distant places in the body to form new tumors (metastasis).

• Benign tumors do not spread, don’t grow back upon removal

• Benign tumors can sometimes be quite large, however. Some can

cause serious symptoms or be life threatening, such as benign
tumors in the brain.
Cancer is characterized by unregulated cell growth and the invasion
and spread of cells from their site of origin.

This leads to the distinction between a benign tumor and a

malignant tumor.

A benign tumor is not evidence of cancer. Benign tumors do not

spread throughout the body (that is, they do not metastasize),
although some can be life threatening
because of their location (e.g. a benign brain tumor that may be
difficult to remove).

Malignant tumors, on the other hand, do not remain

encapsulated, show features of invasion, and metastasize.
 Tissue Changes that Are Not Cancer
Not every change in the body’s tissues is cancer. Some tissue
changes may develop into cancer if they are not treated, however.
Here are some examples of tissue changes that are not cancer.
•Hyperplasia occurs when cells within a tissue multiply faster than
normal and extra cells build up. look normal under a microscope.
•Dysplasia is a more advanced condition than hyperplasia. Extra
cells look abnormal and changes in how tissue organized.

• Some types of dysplasia

may need to be monitored
or treated, but others do
not. An example of
dysplasia is an abnormal
mole (called a dysplastic
nevus).
 Types of Cancer

• There are more than 100 types of cancer.

• Types of cancer are usually named for the organs or
tissues where the cancers form.
For example, lung cancer starts in the lung, and brain
cancer starts in the brain.
• Cancers also may be described by the type of cell
that formed them, such as an epithelial cell (80-
90% ) or a squamous cell.
• The tissue of origin gives the distinguishing
characteristics of the cancer.
Epithelial tissue (epithelium)

Epithelial Cells: These are cells that line the surfaces of organs and
structures throughout the body, such as the skin, blood vessels, and
internal organ cavities like passageways, and forms certain glands.

Epithelium has several different structures, sizes based on their

location and function. Their main functions include protection,
absorption, secretion.
 Squamous cell
These flat cells are found in the tissues that form the surface of the
skin, the passages of the respiratory and digestive tracts, and the
lining of the hollow organs of the body (such as the bladder, kidney,
and uterus, including the cervix).
You can search NCI’s website for information on
• specific types of cancer based on the cancer’s
location in the body
• A to Z List of Cancers.
• Information on childhood cancers and
cancers in adolescents and young adults.
 Cancer Classification
Cancers are classified in two ways:
1. the type of tissue in which the cancer originates
(histological type)
2. primary site, or the location in the body where the cancer
first developed.

The international standard for the classification and

nomenclature of histologies is the International Classification
From a histological standpoint there are hundreds of different
of Diseases for Oncology, Third Edition (ICD-O-3).
cancers, which are grouped into six major categories:

• Carcinoma
• Sarcoma
• Leukemia
• Myeloma
• Lymphoma
• Mixed Types
Carcinoma
Carcinoma refers to a malignant neoplasm of epithelial origin or
cancer of the internal or external lining of the body.
Carcinomas, malignancies of epithelial tissue, account for 80 to
90 percent of all cancer cases.

Carcinomas are divided into two major

subtypes:
i. Adenocarcinoma (gland), and
ii. squamous cell carcinoma, which
originates in the squamous epithelium.

Adenocarcinomas generally occur in

epithelial cells that produce fluids or
mucus. Tissues with this type of
epithelial cell are sometimes called
glandular tissues. Most cancers of the
breast, colon, and prostate are
adenocarcinomas.
Sarcoma

Cancer that originates in supportive and connective tissues such

as bones, tendons, cartilage, muscle, and fat. blood
vessels, lymph vessels

Generally occurring in young adults, the most common sarcoma

often develops as a painful mass on the bone.

Examples of sarcomas are:

Osteosarcoma or osteogenic sarcoma (bone)

Chondrosarcoma (cartilage)
Leiomyosarcoma (smooth muscle)
Rhabdomyosarcoma (skeletal muscle)
Fibrosarcoma (fibrous tissue)
Angiosarcoma (blood vessels)
Liposarcoma (adipose tissue)
Glioma or astrocytoma (neurogenic connective tissue found in
Leukemia

• Cancers that begin in the blood-forming tissue of the bone marrow are
called leukemias.

• Leukemia is a type of cancer found in your blood and bone marrow

and is caused by the rapid production of abnormal white blood cells.

• Also impaired ability of the bone marrow to produce red blood cells
and platelets.

• These cancers do not form solid tumors. Instead, large numbers of

abnormal white blood cells (leukemia cells and leukemic blast cells)
build up in the blood and bone marrow, crowding out normal blood
cells. The low level of normal blood cells can make it harder for the
body to get oxygen to its tissues, control bleeding, or fight infections.
 The Hallmarks of
Cancer

Reprinted and modified from Hanahan, D. and Weinberg, R.A.

(2011).
• Growth signal autonomy:
– Normal cells need external signals from growth factors to divide
– Cancer cells are not dependent on normal growth factor signaling
– Acquired mutations short-circuit growth factor pathways leading to
unregulated growth.

• Evasion of growth inhibitory signals:

– Normal cells respond to inhibitory signals to maintain homeostasis
(most cells of the body are not actively dividing)
– Cancer cells do not respond to growth inhibitory signals
– Acquired mutations or gene silencing interfere with the inhibitory
pathways.

• Avoiding immune destruction (emerging hallmark):

– There is evidence to support the theory of immune surveillance that
states the immune system can recognize and eliminate cancer cells.
– Successful cancer cells may be those that do not stimulate an
immune response or can interfere with the immune response so as to
avoid immune destruction.
• Unlimited replicative potential:
– Normal cells have an autonomous counting device to define a finite
number of cell doublings after which they become senescent. This
cellular counting device is the shortening of chromosomal ends,
telomeres, that occurs during every round of DNA replication
– Cancer cells maintain the length of their telomeres
– Altered regulation of telomere maintenance results in unlimited
replicative potential.
• Tumor-promoting inflammation (an enabling characteristic):
– Virtually all tumors contain inflammatory immune cells
– Inflammation is an immune response that can facilitate the ability of
acquiring the core hallmarks of cancer.
For example, inflammatory cells can provide growth factors and enzymes
that promote angiogenesis and invasion
– In addition, inflammatory cells can release oxygen species that are
mutagenic.
• Invasion and metastasis:
– Normal cells maintain their location in the body and generally do not
migrate
– The movement of cancer cells to other parts of the body is a major
cause of cancer deaths
– Alterations of the genome may affect the activity and/or levels of
enzymes involved in invasion or molecules involved in cell–cell or
• Angiogenesis (formation of new blood vessels):
– Normal cells depend on blood vessels to supply oxygen and nutrients,
but the vascular architecture is more or less constant in the adult
– Cancer cells induce angiogenesis, the growth of new blood vessels,
needed for tumor survival and expansion
– Altering the balance between angiogenic inducers and inhibitors can
activate the angiogenic switch.

• Genome instability and mutation (an enabling

characteristic):
– Acquiring the core hallmarks of cancer usually depends on genomic
alterations
– Faulty DNA repair pathways can contribute to genomic instability.

• Evasion of cell death:

– Normal cells are removed by apoptosis, often in response to DNA
damage
– Cancer cells evade apoptotic signals.

• Reprogramming energy metabolism (emerging

hallmark):
– Uncontrolled cell division demands increases in fuel and biosynthetic
Evidence suggests that cancer is a disease
of the genome at the cellular level
• most agents that cause cancer (carcinogens) cause
alterations to the DNA sequence or mutations (mutagens).
• evidence indicates alterations ranging from single point
mutations to large chromosomal abnormalities, such as
deletions and chromosomal translocations.
• Accumulation of mutations require time  increased risk of
cancer with age , the longer we live the more time there is for
our DNA to accumulate mutations which may lead to cancer.
• However, some tumors evident with a single catastrophic
event in a cell can lead immediately to many mutations and
cause cancer
• Almost all of the mutations identified in tumor cells are
somatic mutations
• Inheritable modifications of the genome and chromatin
structure also play a role in disease of the genome.
 So, is a mutation in the
hemoglobin
gene likely to cause
cancer?

No, because the function of hemoglobin does not affect cell

growth, differentiation, or death and does not lead to
unregulated growth of blood cells.

The hemoglobin gene is not a protooncogene.

 Oncogenes and tumor suppressor
genes
Cell growth is regulated by both positive and negative molecular
factors.
Increased growth requite  positive factors or  negative factors.
There are two major types of mutated genes that contribute to
carcinogenesis:
oncogenes and tumor suppressor genes.
 Oncogene: is a gene mutated such that its protein product is
produced in higher quantities, or has increased activity and
therefore acts in a dominant manner to initiate tumor
formation.
For example, one oncogene produces increased quantities of
a specific growth factor (e.g. platelet-derived growth factor)
which stimulates growth inappropriately.
Another example is an oncogene that produces a growth
factor receptor with increased activity because it has been
altered so that it is always in the “on” state and does not require
growth factor to transduce a signal into the cell.
 Tumor suppressor genes code for proteins that play a role in
 Influential factors in human
carcinogenesis
Environment, diet, and smoking are major factors that play an
important role in carcinogenesis.

These lifestyle factors can, in principle, be altered to prevent

most cancers.

Exposure to carcinogens, hormonal modifications influenced

by childbirth and birth control, and exposure to viruses,
underlie these lifestyle factors..
Environment
Observations by a British surgeon in
1775 resulted in the first correlation
between an environmental agent and
specific cancers.

Percival Pott concluded that the high

incidence of nasal and scrotal cancer in
chimney sweeps was due to chronic
exposure to soot.

UVB radiation, forming pyrimidine

dimers , mutation causing DNA damage
 skin cancer.
 Diet
The incidence of a specific cancer varies greatly between
different populations
in different geographical locations.

Observation of immigration patterns has revealed that local

cancer rates strongly influence cancer risk, with diet.
 Stomach cancer is a predominant cancer in the Japanese
population and a minor cancer in the population of the USA.

Interestingly, the risk of stomach cancer in Japanese people

who have migrated to the USA decreases only if they adopt the
American diet, but not if they retain a Japanese diet.

t
le Die
s ty
an
eric
Am

Ja p
an
ese
st y
le
D iet

Kamineni, A., Williams, M. A., Schwartz, S. M., Cook, L. S., & Weiss, N. S. (1999). The incidence of gastric carcinoma in Asian migrants to the
United States and their descendants. Cancer causes & control : CCC, 10(1), 77–83.
Alcohol
Alcohol was classified as a
carcinogen by the
International Agency for
Research on Cancer in 2007.

There is convincing evidence

that chronic alcohol drinking
increases the risk of cancer
of the mouth, esophagus, and
breast, and probable
evidence for increased risk of
liver cancer.

Chronic alcohol drinking

accounts for 389,000 cases
of cancer worldwide.

Alcohol and smoking have a

 Smoking
• Another lifestyle factors underlying a specific cancer is the
discovery that smoking causes lung cancer (it is also implicated
in pancreatic, bladder, kidney, mouth, stomach, and liver
cancer).
• Since 1985, lung cancer has remained the main cancer
worldwide.
• Smoking accounts for 40% of all cancer deaths: 1.18 million
deaths.
Smoking
• More became
than 8,000 particularly
compounds have been identified in tobacco
fashionable
and tobaccoinsmoke
Europeand
andatthe USA81 carcinogens have been
least
during in
proven World War Ismoke.
cigarette and World War
II and resulted in an epidemic of
lung carcinoma.
• After vast public education
campaigns and a subsequent
reduction of smoking, lung cancer
death rates have fallen dramatically.
• Unfortunately, lung cancer rates are
still rising in most parts of the
https://gco.iarc.fr/today/data/factsheets/populations/586-pakistan-fact-sheets.pdf
 Class Activity

• Lymphoma
Hodgkin lymphoma and Non-Hodgkin lymphoma
• Myeloma and Multiple Myeloma

The presence of Reed-

Sternberg cells in
Hodgkin lymphoma
diagnostically
distinguishes Hodgkin
lymphoma from Non-
Hodgkin lymphoma.