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Updated: Jun 25, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

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

Fangyuan Shao1,2,3, Dongyang Tang1,2, Ling Li1,2

  • 1Cancer Center, Faculty of Health Sciences, University of Macau, Macau SAR, China.

Protein & Cell
|June 23, 2026
PubMed

Insights

Anticancer drugs can cause acute drug protein damage (ADPD), triggering a protein damage response (PDR) in cancer cells. This PDR is a key mechanism driving multidrug resistance (MDR) and offers targets for overcoming treatment failure.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Multidrug resistance (MDR) is a major challenge in cancer therapy, leading to treatment failure and patient mortality.
  • Emerging evidence indicates that anticancer drugs can cause acute drug protein damage (ADPD) to newly synthesized proteins, preceding their action on canonical targets.

Purpose of the Study:

  • To review the biological processes underlying drug resistance.
  • To elucidate the mechanisms of ADPD induced by anticancer drugs.
  • To highlight the role of the protein damage response (PDR) in MDR and its therapeutic potential.

Main Methods:

  • Literature review of current research on drug resistance mechanisms.
  • Analysis of studies investigating ADPD and cellular responses.
  • Synthesis of information on PDR components including ubiquitination, proteasome system, and mitophagy.

Main Results:

  • Anticancer drugs induce ADPD, a process distinct from their intended therapeutic action.
  • Cancer cells activate a PDR involving damage recognition, clearance via the proteasome, and mitophagy.
  • The PDR is identified as a critical factor in the development and progression of MDR.

Conclusions:

  • ADPD and the subsequent PDR are pivotal mechanisms driving MDR in cancer.
  • Understanding these pathways offers novel strategies for predicting and overcoming therapeutic resistance.
  • Targeting PDR components may represent a promising approach to enhance the efficacy of cancer treatments.
Keywords:
ADPDMDRPDRmitochondriamitophagy

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