DNA damage response inhibition‐based combination therapies in cancer treatment: Recent advances and future directions

Aging and Cancer

Tianen Chen¹  Win Topatana¹  Sarun Juengpanich¹  Jiahao Hu¹  Mingyu Chen¹  Shijie Li¹  Xiujun Cai¹  Ziyi Lu¹  Jiasheng Cao¹  Suparat Tongpeng²  Cheeshin Lee³  Yitong Tian³ 

[1] Department of General Surgery Sir Run‐Run Shaw Hospital Zhejiang University School of Medicine Hangzhou Zhejiang P. R. China;School of Ceramic Engineering Institute of Engineering Suranaree University of Technology Nakhon Ratchasima Thailand;School of Medicine Zhejiang University Hangzhou Zhejiang P. R. China;

关键词: cancer therapy;    combination therapy;    DNA damage response;    DNA damage response inhibitors;    DNA repair;    PARP inhibitors;   

DOI  :  10.1002/aac2.12047

来源: DOAJ

【 摘 要 】

Abstract DNA molecules are subject to various lesions that can be detrimental to the cells. DNA damage response (DDR) pathways encompass a variety of mechanisms that cells employ in response to DNA damage. While DDR promotes genomic stability in normal cells, it also protects cancer cells from DNA lesions, particularly against exogenous DNA‐damaging agents. Therefore, DDR pathways can be exploited to account for resistance to chemotherapy and radiotherapy and have the potential to be targeted in cancer treatment. Apart from the poly (ADP‐ribose) polymerase (PARP) inhibitors used in BRCA‐mutant cancers, other DDR inhibitors are being developed and tested in clinical trials. Based on the synthetic lethality theory, combination therapies utilizing DDR inhibitors have been explored and are currently undergoing clinical trials, with promising results in cancer treatment. Combination therapies typically employ a DDR inhibitor to sensitize cancer cells to traditional chemotherapeutic agents, radiotherapy, immunotherapy, and even PARP inhibitors. Herein, we focus on recent advances in DDR inhibitor‐based combination therapies other than PARP inhibitors, explore the advantages and disadvantages of the strategies, and discuss the current challenges and future perspectives.

【 授权许可】

Unknown