2. BASIS OF
CARCINOGENESISCancer is a disease of
uncontrolled growth and
proliferation.
Cells escape the body’s normal
growth control mechanisms and
gain the ability to divide
indefinitely.
Requires the accumulation of
many genetic changes over
time.
3. CRITICAL GENES
These genetic alterations involve activation of proto-oncogenes to oncogenes,
deregulation of tumor suppressor genes and DNA repair genes and ‘immortalisation’
Each new mutation may provide a selective advantage for this cell, leading to ‘clonal
expansion’
ONCOGENES
Genes that promote autonomous cell
growth in cancer cells are
called oncogenes, and their normal
cellular counterparts are called proto-
oncogenes.
Mutation results in GAIN OF FUNCTION
and gene never switches off.
4. Tumour suppressor genes
Antioncogenes, protect cell from becoming tumor, enhances apoptosis of abnormal
cells.
Mutation cause LOSS OF FUNCTION and gene never gets in and remains switched off.
5. TWO HIT HYPOTHESIS
Was given by Knudson.
States that “both copies of a critical gene must be lost from a cell for
a tumor to develop”.
There are
two cases
Hereditary
Sporadic
HEREDITARY
Out of two copies of critical gene, mutation in
one copy is already inherited from family
through vertical gene transfer. Cancer
formation requires mutation in just one left
copy.
SPORADIC
Mutations in both copies of critical genes are to
be occurred by chance as somatic mutations.
6. ROLE OF TELOMERASE
ACTIVITYTelomeres maintain genomic
integrity in normal cells, and
their progressive shortening
during successive cell
divisions induces
chromosomal instability.
In the large majority of
cancer cells, telomere length
is maintained by telomerase.
7. MISMATCH REPAIR AND CANCER
Nothing is perfect, including DNA replication
Our cells have a spell-checker
called mismatch repair (MMR) for this.
MMR is a DNA repair pathway that
primarily repairs DNA errors that arise
during the normal course of DNA
replication and as a result of normal
cellular metabolism.
Without MMR, cells accumulate
mutations at an astronomical rate which
can be a reason for Cancer.
8. METASTASIS
Cancer is such a dangerous not only because it kills but also it has ability to spread from
its primary site to secondary sites in the body and this process is called metastasis.
9. LOCAL
INVASION: Requires to
break down the mechanism
that holds epithelial cells
together.
METASTASIS:
it includes entry of malignant
cells into blood stream or
lymphatic vessels. Colonies
settle down at new secondary
sites and slowly grow more.