The recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.

Autor: Bai YR; Department of Pharmacy, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.; Key Laboratory of Advanced Drug Preparation Technologies, School of Pharmacy, Zhengzhou University, Zhengzhou, China., Yang WG; Department of Pharmacy, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China., Jia R; Department of Pharmacy, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China., Sun JS; Department of Pharmacy, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China., Shen DD; Department of Obstetrics and Gynecology, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment, Zhengzhou, China.; Gynecology Department, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Liu HM; Department of Pharmacy, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.; Key Laboratory of Advanced Drug Preparation Technologies, School of Pharmacy, Zhengzhou University, Zhengzhou, China., Yuan S; Department of Pharmacy, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.; Key Laboratory of Advanced Drug Preparation Technologies, School of Pharmacy, Zhengzhou University, Zhengzhou, China.
Jazyk: angličtina
Zdroj: Medicinal research reviews [Med Res Rev] 2025 Jan; Vol. 45 (1), pp. 214-273. Date of Electronic Publication: 2024 Aug 24.
DOI: 10.1002/med.22069
Abstrakt: Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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