MINI REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1612089
This article is part of the Research TopicMulti-omics Application in Exploring Potential Biomarkers Targeting Resistance of Anti-Cancer Drugs, Volume IIView all 9 articles
Drug-Tolerant Persister (DTP) Cell in Cancer: Reversibility, Microenvironmental Interplay, and Therapeutic Strategies
Provisionally accepted
- 1The Affiliated Hospital of Qingdao University, Qingdao, China
- 2Qingdao Municipal Hospital, Qingdao, Shandong Province, China
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Drug-tolerant persister (DTP) cells are a subpopulation of cancer cells capable of surviving therapeutic stress through reversible, non-genetic adaptations. These cells contribute to minimal residual disease and eventual tumor relapse. Understanding the mechanisms that govern the entry into and exit from the DTP state-such as epigenetic remodeling, metabolic rewiring, and transcriptional plasticity-reveals actionable vulnerabilities. This article reviews the biological basis of DTP reversibility, outlines the major challenges in targeting these cells, and proposes innovative therapeutic strategies including epigenetic inhibitors, metabolic disruptors, and adaptive dosing regimens. We also highlight the importance of biomarker development and dynamic monitoring. Targeting DTP cells at their reversible stage may prevent permanent resistance, offering a promising avenue to improve treatment durability and patient outcomes in cancer therapy.
Keywords: Drug-Tolerant Persister (DTP) Cells, Reversible Drug Resistance, Epigenetic and Metabolic Reprogramming, Tumor microenvironment (TME), Therapeutic Intervention Strategies
Received: 15 Apr 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Li, Xu, Cheng and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haifeng Li, The Affiliated Hospital of Qingdao University, Qingdao, China
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