Grasping cryptic binding sites to neutralize drug resistance in the field of anticancer

Wei-Cheng Yang; Dao-Hong Gong; Hong Wu; Yang-Yang Gao; Ge-Fei Hao

doi:10.1016/j.drudis.2023.103705

Grasping cryptic binding sites to neutralize drug resistance in the field of anticancer

Drug Discov Today. 2023 Sep;28(9):103705. doi: 10.1016/j.drudis.2023.103705. Epub 2023 Jul 13.

Authors

Wei-Cheng Yang¹, Dao-Hong Gong¹, Hong Wu¹, Yang-Yang Gao², Ge-Fei Hao³

Affiliations

¹ National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025, China.
² National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025, China. Electronic address: 1344737702@qq.com.
³ National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025, China; National Key Laboratory of Green Pesticide, Central China Normal University, Wuhan 430079, China. Electronic address: gefei_hao@foxmail.com.

PMID: 37453458
DOI: 10.1016/j.drudis.2023.103705

Abstract

Drug resistance is a significant obstacle to successful cancer treatment. The utilization and development of cryptic binding sites (CBSs) in proteins involved in cancer-related drug-resistance (CRDR) could help to overcome that drug resistance. However, there is no comprehensive review of the successful use of CBSs in addressing CRDR. Here, we have systematically summarized and analyzed the opportunities and challenges of using CBSs in addressing CRDR and revealed the key role that CBSs have in targeting CRDR. First, we have identified the CRDR targets and the corresponding CBSs. Second, we discuss the mechanisms by which CBSs can overcome CRDR. Finally, we have provided examples of successful CBS applications in addressing CRDR. We hope that this approach will provide guidance to biologists and chemists in effectively utilizing CBSs for the development of new drugs to alleviate CRDR.

Keywords: cancer; cryptic binding site; drug design; drug resistance; target drug discovery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Drug Resistance, Neoplasm
Humans
Neoplasms* / drug therapy
Proteins*

Substances

Proteins