Recent progresses in cancer multidrug resistance and therapeutic options associated with protein damage response.

Authors

Fangyuan Shao, Dongyang Tang, Ling Li, Xiaoling Xu, Chu-Xia Deng

Published in

Protein & cell. Jun 23, 2026. Epub Jun 23, 2026.

Abstract

Multidrug resistance (MDR) is a common and leading cause of treatment failure and mortality in cancer patient. While numerous biological processes contribute to drug resistance, recent studies have revealed that most anticancer drugs rapidly bind to and damage newly synthesized proteins upon entering cells. This process, termed acute drug protein damage (ADPD), occurs before the drugs act on their canonical targets. To evade the lethal effects of ADPD, cancer cells rapidly initiate a series of protective responses collectively termed the protein damage response (PDR). This cascade includes damage recognition via protein ubiquitination, damage clearance through the proteasome system, and subsequent mitophagy to remove damaged mitochondria caused by the co-import of drugs and damaged proteins. Here, we review the current understanding of multiple biological processes underlying drug resistance, with a focus on the mechanisms of ADPD induced by anticancer drugs, the pivotal role of PDR in driving MDR, and its potential applications in predicting and overcoming drug resistance.

PMID:
42334959
Bibliographic data and abstract were imported from PubMed on 24 Jun 2026.

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