Topic 10: DNA repair and Cancer

Question 1

how does cancer result

Answer 1

mutation accumulation

normal -> premaligant-> malignant phenotype

Question 2

dna replication stress can stimulate

Answer 2

carcinogenesis - mutation

eg: normal cell -> carcinoma

Question 3

dna damage response prevents

Answer 3

carcinogenesis

Question 4

defects in dna damage responses causes

Answer 4

carcinogenesis

Question 5

what is a key feature of tumours

Answer 5

heterogeneity:
intertumour - different peoples have different tumours
intratumour - within a tumour, tumours are different (many multiple clones)

Question 6

how can different clones occur

Answer 6

• early driver
• mutation accumulation
• clonal expansion (different clones within one tumour)

Question 7

what are heterogenous tumours

Answer 7

consists of different clones and different subclones

Question 8

how can different clones expand

Answer 8

chemotherapy may only target certain clones within the tumour so some may not be targeted and as others are lost, they grow due to differential sensitivity (like antibiotic resistance)

Question 9

how can tumours evolve to consist of more clones

Answer 9

chemotherapy-induced mutations

Question 10

what are synthetic lethality strategies

Answer 10

if normal cell have two pathways in order to survive - one via gene A, other by gene B - allows cell to survive if one pathway is knocked out
if cancer cell - gene A pathway is knocked out by treatement so causes cancer cell to die, gene B pathway is mutated - strategies to target mutated cells but not kill normal cells

Question 11

how is synthetic lethality strategies used in clinical conditions

Answer 11

PARP inhibitor against breast cancers
if normal cells - SSB -> DSB (if PARP inhibitor) but cells can survive due to active BRCA1/2(carrier)
if tumour cells - one clone of tumour does not have BRCA1/2 so other can from DSB (resistant) but this one can’t and can be killed (so sensitive)