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J. Clin. Med. 2019, 8(4), 435; https://doi.org/10.3390/jcm8040435

PARP Inhibitors as a Therapeutic Agent for Homologous Recombination Deficiency in Breast Cancers

1
Division of Cancer Research and Training, Charles Drew University, Los Angeles, CA 90059-2518, USA
2
David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA
*
Author to whom correspondence should be addressed.
Received: 26 February 2019 / Revised: 16 March 2019 / Accepted: 27 March 2019 / Published: 30 March 2019
(This article belongs to the Section Oncology)
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Abstract

Poly (ADP-ribose) polymerases (PARPs) play an important role in various cellular processes, such as replication, recombination, chromatin remodeling, and DNA repair. Emphasizing PARP’s role in facilitating DNA repair, the PARP pathway has been a target for cancer researchers in developing compounds which selectively target cancer cells and increase sensitivity of cancer cells to other anticancer agents, but which also leave normal cells unaffected. Since certain tumors (BRCA1/2 mutants) have deficient homologous recombination repair pathways, they depend on PARP-mediated base excision repair for survival. Thus, inhibition of PARP is a promising strategy to selectively kill cancer cells by inactivating complementary DNA repair pathways. Although PARP inhibitor therapy has predominantly targeted BRCA-mutated cancers, this review also highlights the growing conversation around PARP inhibitor treatment for non-BRCA-mutant tumors, those which exhibit BRCAness and homologous recombination deficiency. We provide an update on the field’s progress by considering PARP inhibitor mechanisms, predictive biomarkers, and clinical trials of PARP inhibitors in development. Bringing light to these findings would provide a basis for expanding the use of PARP inhibitors beyond BRCA-mutant breast tumors. View Full-Text
Keywords: breast cancer; BRCA; BRCAness; PARP; PARP inhibitors; biomarkers; resistance breast cancer; BRCA; BRCAness; PARP; PARP inhibitors; biomarkers; resistance
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Keung, M.Y.T.; Wu, Y.; Vadgama, J.V. PARP Inhibitors as a Therapeutic Agent for Homologous Recombination Deficiency in Breast Cancers. J. Clin. Med. 2019, 8, 435.

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