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PARP Inhibition in Cancer: An Update on Clinical Development

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Abstract

PARP (poly(ADP-ribose) polymerase) inhibitors represent a novel class of anti-cancer therapy; they take advantage of synthetic lethality and induce cell death by exploiting a defect in DNA repair. This class of medication was initially evaluated in patients with BRCA-associated tumors, but efficacy was also demonstrated in other populations. Since 2014, four PARP inhibitors have been approved in various indications: olaparib, niraparib, and rucaparib in high-grade serous ovarian cancer, and olaparib and talazoparib in metastatic breast cancer. The exact indications and study populations vary slightly between the different approvals in both disease states but there is significant overlap. PARP inhibitors continue to be investigated in ongoing clinical trials. In line with other targeted therapies, benefit appears to be strongest in a distinct population of patients with BRCA mutations or other defects in homologous recombination repair. Combination therapies, which include anti-angiogenesis agents and immunotherapy, show promise as a strategy to broaden efficacy for unselected patients. Initial studies of PARP inhibitors in combination with chemotherapy were limited by toxicity, but further studies are underway. To date, head-to-head trials comparing various PARP inhibitors have not been conducted, so questions remain in terms of choosing a PARP inhibitor to administer when indications overlap, as well as how to sequence these medications. Here we review both completed and ongoing clinical trials involving PARP inhibitors and mechanisms of resistance to this class of drugs.

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Authors and Affiliations

  1. Division of Medical Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Esha Sachdev, Roya Tabatabai & Monica M. Mita

  2. Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Varun Roy

  3. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    B. J. Rimel

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  1. Esha Sachdev
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  2. Roya Tabatabai
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Correspondence to Monica M. Mita.

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Esha Sachdev, Roya Tabatabai, Varun Roy, and Monica Mita declare that they have no conflicts of interest that might be relevant to the contents of this article. B.J. Rimel has received consulting fees from Tesaro, Clovis, AstraZeneca, and Genentech.

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Sachdev, E., Tabatabai, R., Roy, V. et al. PARP Inhibition in Cancer: An Update on Clinical Development. Targ Oncol 14, 657–679 (2019). https://doi.org/10.1007/s11523-019-00680-2

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