Figures & data
Figure 1 Synthetic lethality for PARP and BRCA.
Notes: PARP1 is activated by DNA damage (a single-strand break represented by red cross), in the presence of a PARP inhibitor. BER is blocked and, on replication, this single-strand break becomes a double-strand break. In normal healthy cells with functional HRR, this is repaired and the cell survives. In cells with HRR deficiency, ie, through BRCA mutations, the break is not repaired or repaired by error-prone NHEJ or MMEJ resulting in genomic instability and ultimately cell death.
Abbreviations: BER, Base excision repair; BRCA, breast and ovarian cancer susceptibility gene; DSB, DNA double-strand breaks; HRD, HRR deficiency; HRR, homologous recombination repair; MMEJ, microhomology-mediated end-joining; NHEJ, nonhomologous end-joining; PARP, poly(ADP-ribose) polymerase.
Abbreviations: BER, Base excision repair; BRCA, breast and ovarian cancer susceptibility gene; DSB, DNA double-strand breaks; HRD, HRR deficiency; HRR, homologous recombination repair; MMEJ, microhomology-mediated end-joining; NHEJ, nonhomologous end-joining; PARP, poly(ADP-ribose) polymerase.
Table 1 Registration studies for the PARP inhibitors: FDA and EMA approval dates and indications
Table 2 Open and actively recruiting early/late-phase trials with single-agent PARP inhibitors in ovarian cancer (August 2017)
Table 3 PFS/ORR by HRD sub-group with rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 part 1)Citation5
Table 4 Open and actively recruiting trials using PARP inhibitors in combination in ovarian cancer (August 2017)