Namita

1. MOLECULAR
BASIS OF
CANCER
P NAMITA

3. MECHANISM
OF CANCER
CELLS
Monoclonality of tumours
Field theory of cancer
Multistep process of cancer growth and
progression
Genetics theory of cancer
Genetic regulators of normal and abnormal
mitosis

4. 1.Monoclonality of
tumour cells
 Cancers arise from single
clone of cells by genetic
transformation or mutation
 Eg. multiple myeloma -single
type of immunoglobulin is
seen by monoclonal spike in
serum electrophoresis

5. 2.Field theory of cancer
 In an organ only few cells grow into cancer in the
background of other cells
3.Genetic theory of cancer
 In cancer there are either genetic abnormalities in the
cell or normal genes with abnormal expression
4.Multistep process of cancer growth and progression
 Carcinogenesis is a gradual multi-step process involving
many generations of cells
 Various causes of may act on the cell one after the other
,hence called multi-hit process

6. 5.Genetic
regulators of
normal and
abnormal
mitosis
 Proto-oncogenes
 Anti-oncogenes
 Apoptosis regulatory genes
 DNA repair genes

8. EXCESSIVE AND
AUTONOMOUS
GROWTH
 Mutated form of normal protooncogenes in cancer is
called oncogenes
 Overactivity of oncogenes enhances cell proliferation
and development of cancer
 Transformation of proto-oncogene to oncogene occurs
by
• Point mutations-RAS oncogene causing bladder tumour
• Chromosomal translocation- philadelphia chromosome
and burkitts lymphoma
• Gene amplification-ERB-B1 in breast and ovarian cancer

10. REFRACTORINESS TO GROWTH INHIBITION
 The mutation of normal growth suppressor antioncogenes results in
removal of inhibitory effect on cell growth

11. DIFFENCES BETWEEN ONCOGENES AND
ANTI ONCOGENES

12. ESCAPING CELL
DEATH BY
APOPTOSIS
 This is due to mutation in the CD95 receptor or
proapoptotic factors(BAD,BAX,BID and P53)
 MYC oncogene allows cell growth
 Mutated P53 cannot activate proapoptotic factor BAX
reducing apoptosis
 Examples:
 BCL2 gene is mutated in B-cell lymphoma
 CD95 receptors are depleted in hepatocellular
carcinoma

13. AVOIDING
CELLULAR
AGING
 After each mitosis there is shortening
of telomeres
 Telomerase is the RNA enzyme that
helps in DNA repair and maintains
normal telomere length
 In normal cells telomerase activity is
lost after 60-70 mitoses
 While in cancer cells increased
telomerase activity hence avoiding
aging

14. CONTINUED
PERFUSION OF
CANCER:TUMOR
ANGIOGENESIS
 Neovascularisation in cancer supplies nutrients and
oxygen
 Stimulus for angiogenesis is provided by:
 Vascular endothelial growth factor(VEGF)
 Basic fibroblast growth factor(bFGF)
 Anti-angiogenesis factors
 Thrombospondin1
 Angiostatin
 Endostatin
 vasculostatin

15. INVASION
AND DISTANT
METASTASIS
ROUTES OF METASTASIS
Lymphatic spread -carcinomas
Hematogenous spread-sarcomas
Transcoelomic spread

16.  In normal cells if DNA damage is detected it is
repaired before completion of mitosis to maintain
integrity in the genome
 If the DNA repair system is defective unrepaired DNA
is passed to progeny cells resulting in cancer
 Examples
• Lynch syndrome
• Xeroderma pigmentosum
• Ataxia telangiectasia
• Hereditary breast cancer
DNA DAMAGE
AND REPAIR
SYSTEM

17. CANCER PROGRESSION AND
HETEROGENEITY:CLONAL
AGRESSIVENESS
 Clinical parameters of cancer
progression:
 Increasing size of tumour
 Poor differentiation
 Greater anaplasia
 Increased invasiveness and distant
metastasis
 The cancer cells remain monoclonal in
origin but acquire more and more
mutations

18. MULTISTEP
THEORY
 The steps of carcinogenesis are
 Initiation
 Promotion
 Progression

19. MICRO-RNA'S
IN CANCER-
ONCOMIRS
Micro-RNAs are short non-coding
ss RNA transcripts
Normally they function as post-
translational gene regulators
In cancer, they have oncogenic
role in initiation and progression

20. THANK YOU