Recent progress in cancer multidrug resistance and therapeutic options associated with protein damage response
Abstract
Multidrug resistance (MDR) is a common and leading cause of treatment failure and mortality in cancer patients. 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.
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BibTeX
@article{shao2026recent,
title = {{Recent progress in cancer multidrug resistance and therapeutic options associated with protein damage response}},
author = {Fangyuan Shao and Dongyang Tang and Ling Li and Xiaoling Xu and Chu-Xia Deng},
journal = {Protein \& Cell},
year = {2026},
month = jun,
doi = {10.1093/procel/pwag032},
url = {https://doi.org/10.1093/procel/pwag032},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Recent progress in cancer multidrug resistance and therapeutic options associated with protein damage response
AU - Fangyuan Shao
AU - Dongyang Tang
AU - Ling Li
AU - Xiaoling Xu
AU - Chu-Xia Deng
PY - 2026
DA - 2026/06/23
JO - Protein & Cell
DO - 10.1093/procel/pwag032
UR - https://doi.org/10.1093/procel/pwag032
AB - Multidrug resistance (MDR) is a common and leading cause of treatment failure and mortality in cancer patients. 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.
SN - 1674-800X
SN - 1674-8018
ER -