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Combining Poly (ADP-Ribose) Polymerase (PARP) Inhibitors with Chemotherapeutic Agents: Promise and Challenges

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Targeting the DNA Damage Response for Cancer Therapy

Part of the book series: Cancer Treatment and Research ((CTAR,volume 186))

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Abstract

Better understanding of molecular drivers and dysregulated pathways has furthered the concept of precision oncology and rational drug development. The role of DNA damage response (DDR) pathways has been extensively studied in carcinogenesis and as potential therapeutic targets to improve response to chemotherapy or overcome resistance. Treatment with small molecule inhibitors of PARP has resulted in clinical response and conferred survival benefit to patients with ovarian cancer, BRCA-mutant breast cancer, HRD-deficient prostate cancer and BRCA-mutant pancreatic cancer, leading to US Food and Drug Administration (FDA) approvals. However, the observed clinical benefit with single agent PARP inhibitors is limited to few tumor types within the relevant genetic context. Since DDR pathways are essential for repair of damage caused by cytotoxic agents, PARP inhibitors have been evaluated in combination with various chemotherapeutic agents to broaden the therapeutic application of this class of drugs. In this chapter, we discuss the combination of PARP inhibitors with different chemotherapeutics agents, clinical experience to date, lessons learnt, and future directions for this approach.

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Disclosures

KZT

No conflicts of interest.

RT

No conflicts of interest.

SK

Advisory board/consultant for Boehringer Ingelheim, Springworks Therapeutics, Gilead, EcoR1, Seagen, Mundibiopharma, Bayer, Genome & Company, Mirati, OxfordBiotherapeutics, and Harbour Biomed; co-founder and equity holder for PathomlQ, spouse is a scientific advisor for Cadila Pharmaceuticals ltd and founder of Arxeon Inc.

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All the authors have significantly contributed to the preparation of this manuscript and approved the final version.

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Authors and Affiliations

  1. Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA

    Kyaw Zin Thein & Rajat Thawani

  2. DeArmond Endowed Chair of Cancer Research, Division of Hematology and Medical Oncology, Clinical and Translational Research, Knight Cancer Institute (KCI), Center for Experimental Therapeutics (KCI), Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, OC14HO, Portland, OR, 97239, USA

    Shivaani Kummar

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  1. Kyaw Zin Thein
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Correspondence to Shivaani Kummar .

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Editors and Affiliations

  1. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Timothy A. Yap

  2. Dana-Farber Cancer Institute, Boston, MA, USA

    Geoffrey I. Shapiro

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Thein, K.Z., Thawani, R., Kummar, S. (2023). Combining Poly (ADP-Ribose) Polymerase (PARP) Inhibitors with Chemotherapeutic Agents: Promise and Challenges. In: Yap, T.A., Shapiro, G.I. (eds) Targeting the DNA Damage Response for Cancer Therapy. Cancer Treatment and Research, vol 186. Springer, Cham. https://doi.org/10.1007/978-3-031-30065-3_9

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