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REVIEW article

Front. Oncol.
Sec. Cancer Metabolism
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1460412
This article is part of the Research Topic Metabolism, Gut Microbiome, and Cancer View all 6 articles

Application and research progress of synthetic lethality in the development of anticancer therapeutic drugs

Provisionally accepted
Qingyun Yang Qingyun Yang *Xiaoliang Gong Xiaoliang Gong Chunxi Liu Chunxi Liu Haoyang Tang Haoyang Tang SONG WU SONG WU
  • Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

The final, formatted version of the article will be published soon.

    With the tremendous success of the PARP inhibitor olaparib in clinical practice, synthetic lethality has become an important field for the discovery and development of anticancer drugs. More and more synthetic lethality targets have been discovered with the rapid development of biotechnology in recent years. Currently, many drug candidates that were designed and developed on the basis of the concept of synthetic lethality have entered clinical trials. Taking representative synthetic lethal targets Poly ADP-ribose polymerase 1 (PARP1), Werner syndrome helicase (WRN) and protein arginine methyltransferase 5 (PRMT5) as examples, this article briefly discusses the application and research progress of synthetic lethality in the development of anticancer drugs. technology to specifically knock out or inhibit tens of thousands of different genes in thousands of cancer cell lines harboring various genetic alterations (4-6). The dependence of cells carrying different altered genes on specific genes was studied through bioinformatics analysis. After excluding the essential genes necessary for cell survival and proliferation, a large number of synthetic lethal gene pairs were found, and a series of new targets that can be used for precision cancer treatment were identified. In each gene pair (genes A and B), using the highly variable gene A in tumor cells as a marker for tumor patient enrollment and targeting the protein product of gene B to develop specific antitumor drugs achieves specific and potent tumor cell killing without or rarely affecting normal cells (Figure 1). This strategy greatly improves the effectiveness and safety of drugs and provides a new direction for the development of anticancer drugs. In this article, we discuss the application and research progress of synthetic lethality-based anticancer drugs by combining those that have been marketed and those that are currently in clinical trials.

    Keywords: synthetic lethality, precision medicine, PARP, PRMT5, WRN

    Received: 06 Jul 2024; Accepted: 31 Oct 2024.

    Copyright: © 2024 Yang, Gong, Liu, Tang and WU. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qingyun Yang, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.