The mechanisms of multidrug resistance of breast cancer and research progress on related reversal agents

Shiwen Yu; Jinling Zheng; Yan Zhang; Dandan Meng; Yujue Wang; Xiaoyu Xu; Na Liang; Shayibai Shabiti; Xu Zhang; Zixi Wang; Zehua Yang; Pengbing Mi; Xing Zheng; Wenjun Li; Hongfei Chen

doi:10.1016/j.bmc.2023.117486

The mechanisms of multidrug resistance of breast cancer and research progress on related reversal agents

Bioorg Med Chem. 2023 Nov 15:95:117486. doi: 10.1016/j.bmc.2023.117486. Epub 2023 Sep 30.

Authors

Shiwen Yu¹, Jinling Zheng¹, Yan Zhang², Dandan Meng¹, Yujue Wang², Xiaoyu Xu³, Na Liang³, Shayibai Shabiti³, Xu Zhang⁴, Zixi Wang⁴, Zehua Yang², Pengbing Mi², Xing Zheng⁵, Wenjun Li⁶, Hongfei Chen⁷

Affiliations

¹ Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, China Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research [Hunan Provincial Science and Technology Department document (Approval number: 2019-56)], School of Pharmaceutical Science, Hengyang Medical School, University of South China, No.28 Changshengxi Road, Hengyang 421001, PR China; Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nano formulations, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, PR China.
² Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, China Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research [Hunan Provincial Science and Technology Department document (Approval number: 2019-56)], School of Pharmaceutical Science, Hengyang Medical School, University of South China, No.28 Changshengxi Road, Hengyang 421001, PR China.
³ Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nano formulations, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, PR China.
⁴ Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nano formulations, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
⁵ Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, China Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research [Hunan Provincial Science and Technology Department document (Approval number: 2019-56)], School of Pharmaceutical Science, Hengyang Medical School, University of South China, No.28 Changshengxi Road, Hengyang 421001, PR China; Department of Pharmacy, Hunan Vocational College of Science and Technology, Third Zhongyi Shan Road, Changsha, Hunan Province 425101, PR China. Electronic address: 2393628359@qq.com.
⁶ Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nano formulations, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address: wj.li@siat.ac.cn.
⁷ Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, China Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research [Hunan Provincial Science and Technology Department document (Approval number: 2019-56)], School of Pharmaceutical Science, Hengyang Medical School, University of South China, No.28 Changshengxi Road, Hengyang 421001, PR China. Electronic address: hongfeich@163.com.

PMID: 37847948
DOI: 10.1016/j.bmc.2023.117486

Abstract

Chemotherapy is the mainstay in the treatment of breast cancer. However, many drugs that are commonly used in clinical practice have a high incidence of side effects and multidrug resistance (MDR), which is mainly caused by overexpression of drug transporters and related enzymes in breast cancer cells. In recent years, researchers have been working hard to find newer and safer drugs to overcome MDR in breast cancer. In this review, we provide the molecule mechanism of MDR in breast cancer, categorize potential lead compounds that inhibit single or multiple drug transporter proteins, as well as related enzymes. Additionally, we have summarized the structure-activity relationship (SAR) based on potential breast cancer MDR modulators with lower side effects. The development of novel approaches to suppress MDR is also addressed. These lead compounds hold great promise for exploring effective chemotherapy agents to overcome MDR, providing opportunities for curing breast cancer in the future.

Keywords: Breast cancer; Lead compounds; Multidrug resistance.

Publication types

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

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Breast Neoplasms* / drug therapy
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Female
Humans

Substances

Antineoplastic Agents