TDP1 represents a promising therapeutic target for overcoming tumor resistance to chemotherapeutic agents: progress and potential

Meimei Zhang; Ziqiang Wang; Yan Su; Wenbo Yan; Yifan Ouyang; Yanru Fan; Yu Huang; Hao Yang

doi:10.1016/j.bioorg.2024.108072

TDP1 represents a promising therapeutic target for overcoming tumor resistance to chemotherapeutic agents: progress and potential

Bioorg Chem. 2024 Dec 16:154:108072. doi: 10.1016/j.bioorg.2024.108072. Online ahead of print.

Authors

Meimei Zhang¹, Ziqiang Wang¹, Yan Su¹, Wenbo Yan¹, Yifan Ouyang², Yanru Fan³, Yu Huang⁴, Hao Yang⁵

Affiliations

¹ School of Pharmacy, Ningxia Medical University, Yinchuan 750004, PR China.
² Fujian Key Laboratory of Toxicant and Drug Toxicology, School of Medicine, Ningde Normal University, Ningde, Fujian 352100, People's Republic of China. Electronic address: ouyang_pharmacy@163.com.
³ School of Pharmacy, Ningxia Medical University, Yinchuan 750004, PR China; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area Ministry of Education, Ningxia Medical University, Yinchuan 750004, PR China; Collaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Ningxia Characteristic Traditional Chinese Medicine Modern Engineering and Technique Research Center, Ningxia Key Laboratory of Drug Development and Generic Drug Research, Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Yinchuan 750004, PR China. Electronic address: risefyr@163.com.
⁴ School of Pharmacy, Ningxia Medical University, Yinchuan 750004, PR China; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area Ministry of Education, Ningxia Medical University, Yinchuan 750004, PR China; Collaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Ningxia Characteristic Traditional Chinese Medicine Modern Engineering and Technique Research Center, Ningxia Key Laboratory of Drug Development and Generic Drug Research, Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Yinchuan 750004, PR China. Electronic address: huangyunxmu@163.com.
⁵ School of Pharmacy, Ningxia Medical University, Yinchuan 750004, PR China; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area Ministry of Education, Ningxia Medical University, Yinchuan 750004, PR China; Collaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Ningxia Characteristic Traditional Chinese Medicine Modern Engineering and Technique Research Center, Ningxia Key Laboratory of Drug Development and Generic Drug Research, Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Yinchuan 750004, PR China. Electronic address: yhao246@163.com.

PMID: 39705934
DOI: 10.1016/j.bioorg.2024.108072

Abstract

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme that plays a crucial role in repairing DNA lesions caused by the entrapment of DNA topoisomerase IB (TOP1)-DNA break-associated crosslinks. TDP1 inhibitors exhibit synergistic effects with TOP1 inhibitors in cancer cells, effectively overcoming resistance to TOP1 inhibitors. Therefore, this approach presents a promising strategy for reversing tumor resistance to TOP1 inhibitors. This review comprehensively outlines the structural and biological features of TDP1, the substrates involved in its catalytic hydrolysis, and its potential as a therapeutic target in oncology. Additionally, we summarize the various screening methods used to identify TDP1 inhibitors, alongside the latest advancements in TDP1 inhibitor research.

Keywords: Anticancer therapy; Chemotherapy sensitizers; DNA repair; TDP1 inhibitors; TOP1 inhibitors.

Publication types

Review