CANCER

Dr Vijay Marakala,M.DBiochemistry,SIMS&RC.

Cancer is malignant growth (un controlled growth)

and proliferation of cells.

•Uncontrolled growth of a single altered cell. = Mutations = Cancer•Cancer cells grow faster, adapt better.•They live at the cost of our living.

Normal cells Mutated cells Proliferation of mutated cells

Uncontrolled growth Invasion Metastasis

MORPHOLOGICAL CHANGES IN CANCER CELL

Multilayer

Growth

Grow over one

another

Motility

Rounder

Shape

Due to loss of contact inhibition

BIOCHEMICAL CHANGES IN CANCER CELL

Altered synthesis of

certain growth factors

Lactic acidosis

↓Catabolism of

pyrimidines

↑Synthesis of DNA and

RNA

Altered gene regulation

Stimulates anabolic processes

NOMENCLATURE AND CLASSIFICATION OF CANCERS

CarcinomasCancer of cells or organs

derived from either ectoderm or endoderm

Cancers of epithelial tissues, nervous tissues,

glands etc

SarcomasCancers of tissues of mesodermal origin

Cancers of bone, cartilage, connective

tissue, muscle etc

B/O the 3 embryonic germ layers from which tissue or organ is derived

NOMENCLATURE AND CLASSIFICATION OF CANCER

CarcinomasAdenocarcinoma

Squamous cell carcinoma

Gliomas

Sarcomas

Osteosarcoma

Fibrosarcoma

CAUSES FOR CANCER

EstrogenOCP

Anabolic steroids

Hormonal

Hepatitis B virus

Retro viruses

Biological

Cigarette smoke

Aflatoxins

Chemical

X-raysγ-rays

UV rays

Physical

MECHANISM OF CARCINOGENESIS

Radiation Damage to DNA

Direct effect

• Single or double strand breaks• Elimination of purine/pyrimidine bases• Cross-linking of strands• Formation of pyrimidine dimers

Indirect effects

• Production of free radicals

MECHANISM OF CHEMICAL CARCINOGENS

• Carcinogens are generally electrophiles

• Electrophiles readily attack nucleophilic group of DNA

• Carcinogens may bind covalently to cellular DNA

Direct acting Procarcinogens

Target DNA

MECHANISM OF CHEMICAL CARCINOGENS

Procarcinogens

Procarcinogens Proximate carcinogens

Ultimate carcinogens

MECHANISM OF BIOLOGICAL CARCINOGENS

ONCOGENIC VIRUSES

Virus infect host cell

DNA virus binds tightly to host cell DNA

Altered gene expression

Altered protein [oncoprotein]

MECHANISM OF HORMONAL CARCINOGENS

• Endometrial carcinoma

Estrogen

• Breast cancer

OCP

• Liver carcinoma

Anabolic steroids

MOLECULAR BASES OF CANCER

• Normal genes which inhibit cell division

Tumor suppressor gene

• Normal genes which stimulate cell division

Proto-oncogene

• Genes capable of causing cancer

Oncogenes

Balance and imbalance between factors stimulating and inhibiting cell growth

Inhibitors-

Stimulators+

Tumour supressor

gene

Proto-oncogene

Inhibitors-

Stimulators+ +

oncogenes

Oncogenes

Tumour supressor

gene

ACTIVATION OF PROTO-ONCOGENE TO ONCOGENE

Viral insertion into chromosome

Chromosomal translocation

Gene amplification

Point mutation