hallmarks of cancer Flashcards
what things has the study of cancer made us know more about?
growth of normal cells
pathways controlling normal growth
mechanisms of cell death
mechanisms of tissue regeneration
what does cancer imply?
- uncontrolled growth
- capacity to infiltrate or damage normal tissues
- capacity to spread to other sites
- capacity to cause illness and/or death
what are the 6 hallmarks of cancer
- autonomy from growth signals
- evasion of growth inhibitory signals
- evasion of apoptosis
- unlimited replicative potential
- angiogenesis
- invasion and metastasis
where do mutations have to occur for cancer to be inherited?
germline
which viral infections are associated to which cancer?
HPV 16 & 18 - cervical carcinoma
HTLV-1 - adult T cell lymphoma
EBV - Burkitt’s lymphoma
Hepatitis B & C - hepatocellular carcinoma
why can chemotherapy and chemical carcinogens cause cancer?
- interact with components of DNA to cause damage
- damage may be to bases or sugar-phosphate backbone
- damage may be repaired, misrepaired or unrepaired
- unrepaired or misrepaired damage that does not trigger cell death will be passed on to daughter cells
what do oncogene mutations lead to?
- affect expression of proteins involved with pathways associated with cancer
- pathways for growth differentiation and cell death
- mutated genes and their products become overactive
what type of mutation occurs in tumour suppressor genes in cancer?
loss of function
what are oncogenes?
oncogenes are often mutated versions of normal human genes (proto-oncogenes)
mutations may affect gene function in various ways
what are the effects of oncogenes
increase activity of pro-malignant pathways:
cell growth, replication, angiogenesis
invasion, metastasis
inhibit activity of anti-malignant pathways:
apoptosis, cell cycle regulation, growth inhibition
what are 3 examples of oncogenes?
- erbB1 encodes the EGFR receptor-> result is over-activity of RAS - MAPK pathway and over-expression of growth promoting genes
- erbB2 is amplified in about 25% of breast cancers
Her2 is over-expressed in these cancers - Ras- mutated in 30% of cancers
what is the inheritance pattern of oncogenes?
dominant
what is the inheritance pattern if tumour suppressor genes?
recessive
what are 2 tumour suppressor genes?
- P53 mutated in 1/2 cancers
- APC- FAP and increased colorectal cancer
what syndrome do you get with mutated gremlin p53?
Li-Fraumeni syndrome:
grossly elevated cancer risk
sarcoma, breast cancer, leukaemia, brain tumours at an early age
what doe APC mutation inhibit?
B- catenin
results in proliferation
what are the 3 gees associated with apoptosis?
Bcl-2 anti-apoptotic
Bax pro-apoptotic
p53 pro-apoptotic
how do cancer cells gain unlimited replicative potential?
- telomerase inactive in most normal tissues
- telomerase upregulated in most tumour cells- increasing size of telomeres reduces the chance of cell senescence
- proteins that activate telomerase contribute to malignant transformation
how are cancer cells able to induce angiogenesis?
angiogenesis stimulated by hypoxia in normal tissues and tumours
Vascular Endothelial Growth Factor (VEGF) major stimulant VEGF upregulated in many tumours
how are cancer cells able to invade and metastasise?
-tumour cells can break free from inter- and extra-cellular connections via abnormal expression of integrins
invasive capacity mediated by matrix metalloproteases (MMPs) and inhibited by TIMPs - abnormal balance in tumour cells
what are 2 emerging hallmarks of cancer?
- deregulating cellular energetics
2, avoiding immune destruction
what are 2 enabling characteristics of cancer?
- genome instability
- tumour promoting inflammation
