Molecular Carcinogenesis Flashcards
what are the specific hallmarks of cancer cells (10)
self sufficiency in positive growth signalling - eg in RAS always on
evading growth suppressors - mutations in Rb to stop prevention of proliferation
avoiding immune destruction - binding PD1/PDL1 stops T cells
enabling replicative immortality - stop telomere shortening
promoting inflammation
activating invasion and metastasis
inducing angiogenesis - nutrients for tumour
genome instability and mutation (Bcl2 overexpression in cancers = anti-apoptotic)
resisting cell death
deregulated metabolism
what is a proto-oncogene
normal genes that promote cell proliferation, survival and angiogenesis
what is an oncogene
mutation of protocol-oncogene causing cancerous cell - activity of expressed proteins
why are oncogenes so powerful genetically
dominant gain in function
1 mutant copy of gene acts dominantly to the remaining normal parental gene
what are some examples of oncogenes
RAS, myc, RAF, HER2 and EGFR
what are the 4 steps mechanisms of oncogene activation
translocation
point mutation
amplification
insertion
describe the specific 4 processes of oncogene activation
trasnlocaiton of oncogene from low to an active transcription site - aberrant expression of the oncogene
point mutation - substitution of single base within the amino acid sequence produces a hyperactive oncoprotein
amplification by insertion of multiple copies of an oncogene - increased expression
insertion for promoter or enhancing genes near an oncogene = increased expression
what are the two types of tumour suppressor gene
gatekeeper - antioncogenes - negative regulators of the cell eye and proliferation - positive regulators of apoptosis
caretakers - maintain genetic stability
what are some examples of tumour suppressor genes
APC, P53, BRCA1/2
what is the mechanism of TSG loss
carcinogens induce molecular abnormalities in TSG/s which reduction protein function / expression
does this by inactivating point mutations, deletion, translocations, epigenetic silencing
what are familial cancer syndromes
caused by inheritance of a mutant copy of TSG gene which increases risk by 70-90%
how would familial transfer of a mutant caretaker gene lead to increased risk of cancer
genetic instability - predisposition to developing cancer - also needs to hit hypothesis
what is required to turn a normal cell into a neoplastic cell
minimum of 3-6 genetic alterations
describe the mutagenic pathway of colorectal cancer from normal epithelium to adenocarcinoma
normal (APC) early adenoma (KRAS) intermediate adenoma (SMAD4) late adenoma (P53) adenocarcenoma
what are the uses of tumour markers
diagnosis - identification of type or subtype
prognosis - some confer worse survival
therapy - predict therapeutic response
monitoring
what are serum markers and what can they be used for
antigens of cancerous cells - not sensitive or specific enough for general screening but can be used as an adjunct (antra help)
why types of cancerous cells can serum markers test for
AFP, hCG, PSA (prostate), CEA and thyroglobulin
what marker is over expressed in 30% of breast cancers and how do we use this in treatment
HER2 - treat with herceptin
what mutations do 50% of colorectal cancers have and how do we use this in treatment
KRAS mutation - permanently on from of RAS
therefore cannot give cetuximab or panitummuab
what protein is over expressed in lung cancers
EGFR
