Open AccessTargeting DNA repair pathway in cancer: Mechanisms and clinical application
Author(s) -
Wang Manni,
Chen Siyuan,
Ao Danyi
Publication year - 2021
Publication title -
medcomm
Language(s) - English
Resource type - Journals
ISSN - 2688-2663
DOI - 10.1002/mco2.103
Subject(s) - genome instability , dna damage , dna repair , cancer , dna damage repair , cancer research , biology , cancer cell , wee1 , synthetic lethality , medicine , dna , genetics , cell cycle , cyclin dependent kinase 1
Abstract Over the last decades, the growing understanding on DNA damage response (DDR) pathways has broadened the therapeutic landscape in oncology. It is becoming increasingly clear that the genomic instability of cells resulted from deficient DNA damage response contributes to the occurrence of cancer. One the other hand, these defects could also be exploited as a therapeutic opportunity, which is preferentially more deleterious in tumor cells than in normal cells. An expanding repertoire of DDR‐targeting agents has rapidly expanded to inhibitors of multiple members involved in DDR pathways, including PARP, ATM, ATR, CHK1, WEE1, and DNA‐PK. In this review, we sought to summarize the complex network of DNA repair machinery in cancer cells and discuss the underlying mechanism for the application of DDR inhibitors in cancer. With the past preclinical evidence and ongoing clinical trials, we also provide an overview of the history and current landscape of DDR inhibitors in cancer treatment, with special focus on the combination of DDR‐targeted therapies with other cancer treatment strategies.