Module3 Flashcards
Which of the following DNA-repair mechanisms is a high fidelity process to repair double stranded DNA breaks?
HR
PARP is involved in repairing single stranded DNA breaks?
True
Synthetic Lethality means what?
when 2 non-lethal genetic events occur that individually may not have a deleterious effect on the cell, but when combined can cause cell death
In BRCA1/BRCA2 mutated cells, repair of double strand DNA breaks is forced down the error prone ________________ pathway.
NHEJ
Which of the following is a proposed mechanism of action of PARP inhibitors?
Prevention of BER mediated single strand DNA repair via inhibition of PARP/ PARP trapping
According to the NCCN guidelines, patients w advanced prostate cancer should have genetic testing to detect germline or somatic mutations in which of the following genes?
BRCA1, BRCA2, ATM, RAD51
Rucaparib inhibits which PARP enzymes?
PARP -1, -2 AND -3
What DNA repair mutations could patients in Triton2 have?
BRCA1, BRCA2, ATM, CHEK2, or other specified mutations
What % of patients w measurable disease and a BRCA1, or BRCA2 mutation had a confirmed radiographic response in Triton2?
44%
What percentage of patients w BRCA1, or BRCA2 mutation and confirmed objective response had duration of response > 6 months in Triton2?
56%
What were 3 common AE’s among patients w BRCA1/BRCA2 mutation in Triton2?
Asthenia/fatigue, nausea, anemia
What DNA repair gene mutations could patients in Triton3 have?
Only BRCA1, BRCA2, or ATM
In the phase 3 PROfound trial olaparib was compared to what therapy?
tmt of physician’s choice (abiraterone, or enzalutamide)
In PROfound what were the median rPFS duration for olaparib and the control arm among patients w BRCA1, BRCA2, or ATM mutation?
7.4 months vs. 3.6 months
In PROfound, what was the confirmed ORR in the olaparib and control arms among patients w BRCA1, BRCA2, or ATM mutation and measurable disease?
33% vs. 2%
