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
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
9.
10. REFRACTORINESS TO GROWTH INHIBITION
The mutation of normal growth suppressor antioncogenes results in
removal of inhibitory effect on cell growth
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
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
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