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PARP molecular functions and applications of PARP inhibitors in cancer treatment

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Abstract

Poly(ADP-ribosyl)ation (PARylation), a type of post-translational modification catalyzed by poly(ADP-ribose) polymerase (PARP), is implicated in numerous biological processes including DNA repair, chromatin remodeling, programmed cell death, RNA regulation, and PAR-dependent ubiquitination. The advent of PARP inhibitors represents a new synthetic lethality paradigm for killing tumors bearing BRCA mutations in which tumor-specific defects are exploited to create a vulnerability that causes tumor cell death. To date, four PARP inhibitors have been approved by the US Food and Drug Administration for treatment of several types of cancer. In this review, we summarize the current knowledge of the molecular functions of PARP1 and highlight the recent advances in the use of PARP inhibitors in cancer treatment and the problem of drug resistance.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (T2225006) and Beijing Municipal Natural Science Foundation (Z220011) to ML.

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Authors and Affiliations

  1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China

    Yuhan Guo, Boyang Fan & Mo Li

  2. National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China

    Mo Li

  3. Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, 100191, China

    Mo Li

  4. Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China

    Mo Li

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ML designed and wrote the manuscript. YG wrote the manuscript. BF revised the manuscript.

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Guo, Y., Fan, B. & Li, M. PARP molecular functions and applications of PARP inhibitors in cancer treatment. GENOME INSTAB. DIS. 4, 137–153 (2023). https://doi.org/10.1007/s42764-023-00100-w

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