CANCER
Classification , etiology and
pathogenesis
Harshita Parab – 56
Nikita Pardeshi -57
Kalyani Patil – 58
Srushti Patil – 59
Neha Pawar- 60
• The term ‘neoplasia’ means new growth; the new
growth produced is called ‘neoplasm’ or ‘tumour’.
• Definition of a neoplasm or tumour is ‘a mass of
tissue formed as a result of abnormal, excessive,
uncoordinated, autonomous and purposeless
proliferation of cells even after cessation of
stimulus for growth which caused it ’ .
• Neoplasms may be ‘benign’ when they are slow-
growing and localised without causing much
difficulty to the host, or ‘malignant’ when they
proliferate rapidly, spread throughout the body and
may eventually cause death of the host. The
common term used for all malignant tumours is
cancer.
CLASSIFICATION OF CANCER
Cancers are classified in two ways: by the type of
tissue in which the cancer originates ( histological
type) or the location in the body where the cancer
first developed.
From the histological standpoint the cancer are
grouped into six major categories.
1. Carcinoma
2. Sarcoma
3. Myeloma
4. Leukemia
5. Lymphoma
6. 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:
adenocarcinoma, which
develops in an organ or gland,
and squamous cell carcinoma,
which originates in the
squamous epithelium.
Sarcoma
Sarcoma refers to cancer that
originates in supportive and
connective tissues such as bones,
tendons, cartilage, muscle, and fat.
Generally occurring in young
adults, the most common sarcoma
often develops as a painful mass
on the bone. Sarcoma tumors
usually resemble the tissue in
which they grow.
Examples of sarcomas are:
Osteosarcoma or osteogenic
sarcoma (bone)
Chondrosarcoma (cartilage)
Leiomyosarcoma (smooth muscle)
Myeloma
Myeloma is cancer
that originates in
the plasma cells of
bone marrow. The
plasma cells
produce some of
the proteins found
in blood.
Leukemia
Leukemias ("liquid cancers" or "blood
cancers") are cancers of the bone
marrow (the site of blood cell
production). The word leukemia means
"white blood" in Greek. The disease is
often associated with the
overproduction of immature white
blood cells. These immature white
blood cells do not perform as well as
they should, therefore the patient is
often prone to infection. Leukemia also
affects red blood cells and can cause
poor blood clotting and fatigue due to
anemia.
Examples of leukemia
include:Myelogenous or granulocytic
leukemia (malignancy of the myeloid
and granulocytic white blood cell series)
Lymphoma
Lymphomas develop in the glands or
nodes of the lymphatic system, a
network of vessels, nodes, and organs
(specifically the spleen, tonsils, and
thymus) that purify bodily fluids and
produce infection-fighting white blood
cells, or lymphocytes. Unlike the
leukemias which are sometimes called
"liquid cancers," lymphomas are "solid
cancers." Lymphomas may also occur
in specific organs such as the stomach,
breast or brain. These lymphomas are
referred to as extranodal lymphomas.
The lymphomas are subclassified into
two categories: Hodgkin lymphoma
and Non-Hodgkin lymphoma. The
presence of Reed-Sternberg cells in
Hodgkin lymphoma diagnostically
distinguishes Hodgkin lymphoma from
Non-Hodgkin lymphoma.
Mixed types
The type components may be
within one category or from
different categories.
Some examples are:
adenosquamous carcinoma
mixed mesodermal tumor
Carcinosarcoma
teratocarcinoma
Etiological agents
1. ENVIRONMENTAL AGENTS
• Tobacco, smokes,diets,environmental pollutants,etc
• Heavy smoking,cause lung,oral cavity and oesophagus cancer
• Excessive intake of alcohol cause liver cancer
2. CHEMICAL CARCINOGEN
• Nickel compounds,cadmium,arsenic,nitrosamines,trichloroethylene
3. PHYSICAL CARCINOGEN
• Uv rays, ionizing radiations(x-rays and gamma rays)
4. BIOLOGICAL CARCINOGEN
• Virus has also been associated with various types of cancer this
viruses are called oncoviruses.
• Hepatitis B and C virus is casually related with hepatocellular
carcinoma
5. ENDOGENOUS FACTORS
• mutation, change in DNA replication, metabolic
reactions generating, reactive oxygen radicals,
immunosystem defects, ageing
PATHOGENESIS OF CANCER
• The induction of cancer by chemical carcinogens occurs
after a delay—weeks to months in the case of experi
mental animals, and often several years in humans.
• Other factors that influence the induction of cancer are
the dose and mode of administration of carcinogenic
chemical, individual susceptibility and various predis
posing factors.
• Chemical carcinogenesis occurs by induction of mutation
in the proto-oncogenes and anti-oncogenes.
• The phenomena of cellular transformation by chemical
carcinogens (as also other carcinogens) is a progressive
process involving 3 sequential stages initiation Promotion
Progression
Pathogenesis of Cancer
Initiation of Carcinogenesis
1. Metabolic activation
• Vast majority of chemical carcino gens are indirect-acting or procarcinogens
requiring metabolic activation, while direct-acting carcinogens do not require this
activation.
• The indirect-acting carcinogens are activated in the liver by the mono-oxygenases
of the cytochrome P-450 system in the endoplasmic reticulum.
• In some circum stances, the procarcinogen may be detoxified and rendered
inactive metabolically. In fact, following 2 requirements determine the carcino
genic potency of a chemical:
i) Balance between activation and inactivation reaction of the carcinogenic chemical.
ii) Genes that code for cytochrome P-450-dependent enzymes involved in metabolic
activation e.g a genotype carrying susceptibility gene CYP1A1 for the enzyme system
has far higher incidence of lung cancer in light smokers as compared to those not
having this permissive gene. Besides these two, additional factors such as age, sex
and nutritional status of the host also play some role in determining response of the
individual to chemical carcinogen.
2. Reactive electrophiles While direct-acting carcinogens are intrinsically
electrophilic, indirect-acting substances become electron-deficient after
metabolic activation i.e. they become reactive electro philes.
• Following this step, both types of chemical carcinogens behave alike and
their reactive electrophiles bind to electron-rich portions of other molecules
of the cell such as DNA, RNA and other proteins.
3. Target molecules The primary target of electro philes is DNA, producing
mutagenesis. The change in DNA may lead to ‘the initiated cell’ or some form
of cellular enzymes may be able to repair the damage in DNA.
• The classic example of such a situation occurs in xero dermapigmentosum, a
precancerous condition, in which there is hereditary defect in DNA repair
mechanism of the cell and thus such patients are prone to develop skin
cancer.
• The carcinogenic potential of a chemical can be tested in vitro by Ames’ test
for mutagenesis (described later). Any gene may be the target molecule in
the DNA for the chemical carcinogen
• However, on the basis of chemically induced cancers in experimental
animals and epidemiologic studies in human beings, it has been observed
that most frequently affected growth promoter oncogene is RAS gene
mutation and anti oncogene (tumour suppressor) is p53 gene mutation.
• 4. The initiated cell The unrepaired damage produced in
the DNA of the cell becomes permanent and fixed only if
the altered cell undergoes at least one cycle of
proliferation.
• This results in transferring the change to the next pro
geny of cells so that the DNA damage becomes
permanent and irreversible, which are the characteristics
of the initiated cell, vulnerable to the action of promo
ters of carcinogenesis.
• The stimulus for proliferation may come from
regeneration of surviving cells, dietary factors, hormone-
induced hyper plasia, viruses etc.
• A few examples are the occurrence of hepatocellular
carcinoma in cases of viral hepatitis, association of
endometrial hyperplasia with endometrial carcinoma,
effect of oestrogen in breast cancer.
Promotion of Carcinogenesis
Promotion is the next sequential stage in the chemical carcino genesis.
Promoters of carcinogenesis are sub stances such as phorbol esters, phenols,
hormones, arti ficial sweeteners and drugs like phenobarbital. They differ from
initiators in the following respects:
i) They do not produce sudden change.
ii) They require application or administration, as the case may be, following
initiator exposure, for sufficient time and in sufficient dose.
iii) The change induced may be reversible.
iv) They do not damage the DNA per se and are thus not mutagenic but instead
enhance the effect of direct-acting carcinogens or procarcinogens.
v) Tumour promoters act by further clonal proliferation and expansion of initiated
(mutated) cells, and have reduced requirement of growth factor, especially after
RAS gene mutation.
It may be mentioned here that persistent and sustained application/exposure of
the cell to initiator alone unassociated with subsequent application of promoter
may also result in cancer. But the vice versa does not hold true since neither
application of promoter alone, nor its application prior to exposure to initiator
carcinogen, would result in transformation of target cell
Progression of Carcinogenesis
• Progression of cancer is the stage when mutated
proliferated cell shows phenotypic features of
malignancy.
• These features pertain to morphology, biochemical
composition and molecular features of malignancy.
• Such phenotypic features appear only when the
initiated cell starts to proliferate rapidly and in the
process acquires more and more mutations.
• The new progeny of cells that develops after such
repetitive proliferation inherits genetic and
biochemical characteristics of malignancy.
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