TY - CHAP
T1 - Combining Poly (ADP-Ribose) Polymerase (PARP) Inhibitors with Chemotherapeutic Agents
T2 - Promise and Challenges
AU - Thein, Kyaw Zin
AU - Thawani, Rajat
AU - Kummar, Shivaani
N1 - Publisher Copyright:
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - BReast CAncer gene BRCA 1/2
KW - Chemotherapeutics
KW - DNA damage response (DDR) pathway
KW - Homologous recombination (HR) repair
KW - Poly (ADP-ribose) polymerase (PARP) inhibitors
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U2 - 10.1007/978-3-031-30065-3_9
DO - 10.1007/978-3-031-30065-3_9
M3 - Chapter
C2 - 37978135
AN - SCOPUS:85177504731
T3 - Cancer Treatment and Research
SP - 143
EP - 170
BT - Cancer Treatment and Research
PB - Springer Science and Business Media Deutschland GmbH
ER -