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. 2023:186:143-170.
doi: 10.1007/978-3-031-30065-3_9.

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

Kyaw Zin Thein  1 , Rajat Thawani  1 , Shivaani Kummar  2
Affiliations

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

Kyaw Zin Thein et al. Cancer Treat Res. 2023.

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.

Keywords: BReast CAncer gene BRCA 1/2; Chemotherapeutics; DNA damage response (DDR) pathway; Homologous recombination (HR) repair; Poly (ADP-ribose) polymerase (PARP) inhibitors.

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References

    1. Lu Y et al (2018) Double-barreled gun: combination of PARP inhibitor with conventional chemotherapy. Pharmacol Ther 188:168–175 - PubMed - PMC - DOI
    1. Dias MP et al (2021) Understanding and overcoming resistance to PARP inhibitors in cancer therapy. Nat Rev Clin Oncol 18(12):773–791 - PubMed - DOI
    1. Li H et al (2020) PARP inhibitor resistance: the underlying mechanisms and clinical implications. Mol Cancer 19(1):107 - PubMed - PMC - DOI
    1. Howard SM, Yanez DA, Stark JM (2015) DNA damage response factors from diverse pathways, including DNA crosslink repair, mediate alternative end joining. PLoS Genet 11(1):e1004943 - PubMed - PMC - DOI
    1. Cerrato A, Morra F, Celetti A (2016) Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR defects: the rationale for their inclusion in the clinic. J Exp Clin Cancer Res 35(1):179 - PubMed - PMC - DOI

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