Review Article

Predictors and Modulators of Synthetic Lethality: An Update on PARP Inhibitors and Personalized Medicine

Table 1

PARP inhibitors currently undergoing development.

PARP inhibitorsTumor typesMost advanced developmental stage in progressKey clinical trialsReferences

OlaparibFDA approved for ovarian cancer
Being tested for breast, prostate, and pancreatic cancers
FDA approvedPhase II trial found that Olaparib monotherapy in patients with BRCA1/2 mutated ovarian cancer following ≥3 chemotherapy treatments resulted in 31% response rate
Phase II trial found that Olaparib maintenance therapy in patients with platinum- (Pt-) sensitive recurrent serous ovarian cancer with mutated BRCA1/2 resulted in median progression free survival of 6.9 months longer than those receiving placebo
[150, 151]

TalazoparibBeing tested for ovarian, breast, and various advanced/metastatic solid cancers (primary peritoneal carcinoma, fallopian tube carcinoma, etc.)Phase IIIPhase II trial for Talazoparib monotherapy in patients with deleterious BRCA1/2 mutated ovarian cancer who had prior PARP inhibitor treatment currently recruiting
Phase III trial for Talazoparib monotherapy in patients with BRCA1/2 mutated, advanced, or metastatic breast cancer currently recruiting
[152, 153]

VeliparibBeing tested for breast, pancreatic, non-small-cell lung cancers, lymphoma, and multiple myeloma, mostly in combination with chemotherapyPhase IIIPhase I/II trial of Veliparib and Topotecan for relapsed ovarian cancer of negative or unknown BRCA status completed
Phase II trial of Veliparib alone or with Gemcitabine and Cisplatin in patients with locally advanced or metastatic pancreatic cancer currently recruiting
Phase I/II trial for Veliparib, Bendamustine HCl, and Rituximab in patients with relapsed lymphoma and multiple myeloma completed
[154156]

RucaparibBeing tested for ovarian and pancreatic cancersPhase IIIPhase III trial for Rucaparib maintenance therapy in patients with Pt-sensitive recurrent ovarian cancer, fallopian tube, or primary peritoneal cancers currently recruiting
Phase II trial for Rucaparib monotherapy in patients with BRCA1/2 mutated, locally advanced, or metastatic pancreatic cancer currently ongoing
[157, 158]

NiraparibBeing tested for ovarian and breast cancers and Ewing sarcomaPhase IIIPhase III trial for Niraparib monotherapy in patients with HER2 negative, BRCA1/2 mutated breast cancer currently recruiting
Phase II trial for Niraparib monotherapy in patients with ovarian cancer following ≥3 chemotherapy treatments currently recruiting
[159161]