Erasing the invisible: targeting persister cells to cure minimal residual disease
5 affiliations
- 1Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital
- 2Department of Big Data in Health Science, School of Public Health and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine
- 3Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
- 4Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital
- 5Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer
Abstract
Despite revolutionary advances in immunotherapy and targeted therapies, tumor recurrence driven by minimal residual disease (MRD) and drug-tolerant persister (DTP) cells remains a critical challenge in oncology. MRD, a reservoir of residual cancer cells undetectable by conventional imaging but identifiable via sensitive molecular techniques like next-generation sequencing and ctDNA analysis, serves as a prognostic biomarker for relapse across hematologic and solid malignancies. Within MRD, DTP cells, characterized by transient drug tolerance, evade therapies through adaptive mechanisms such as quiescence, metabolic reprogramming, epigenetic modifications, and signaling pathway activation. These cells, pivotal in mediating therapeutic resistance, dynamically evolve from reversible tolerance to stable resistance, fueling disease relapse. This review elucidates the clinical significance of MRD and DTP cells, detailing their biological characteristics, detection technologies, and formation mechanisms. We highlight therapeutic strategies targeting DTP cells, including pathway inhibitors, epigenetic modulators, and autophagy blockers, to reverse MRD and prevent recurrence. Challenges in translating these approaches to clinical practice, such as DTP heterogeneity and biomarker development, are addressed alongside emerging technologies like single-cell omics and AI-driven analytics. By integrating mechanistic insights with innovative detection and therapeutic strategies, targeting DTP cells within MRD holds transformative potential to enhance long-term cancer outcomes.
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BibTeX
@article{wang2026erasing,
title = {{Erasing the invisible: targeting persister cells to cure minimal residual disease}},
author = {Yu Wang and Zijian Shi and Fangquan Xu and Yun Zhu and Chao Liu and Bo Wang and Ning Ji and Zhenduo Wang and Sinan Wang and Xuan Zhou and Yu Ren},
journal = {Holistic Integrative Oncology},
year = {2026},
month = oct,
doi = {10.1007/s44178-026-00307-3},
url = {https://doi.org/10.1007/s44178-026-00307-3},
note = {CC BY},
}
RIS
TY - JOUR
TI - Erasing the invisible: targeting persister cells to cure minimal residual disease
AU - Yu Wang
AU - Zijian Shi
AU - Fangquan Xu
AU - Yun Zhu
AU - Chao Liu
AU - Bo Wang
AU - Ning Ji
AU - Zhenduo Wang
AU - Sinan Wang
AU - Xuan Zhou
AU - Yu Ren
PY - 2026
DA - 2026/10/25
JO - Holistic Integrative Oncology
DO - 10.1007/s44178-026-00307-3
UR - https://doi.org/10.1007/s44178-026-00307-3
AB - Despite revolutionary advances in immunotherapy and targeted therapies, tumor recurrence driven by minimal residual disease (MRD) and drug-tolerant persister (DTP) cells remains a critical challenge in oncology. MRD, a reservoir of residual cancer cells undetectable by conventional imaging but identifiable via sensitive molecular techniques like next-generation sequencing and ctDNA analysis, serves as a prognostic biomarker for relapse across hematologic and solid malignancies. Within MRD, DTP cells, characterized by transient drug tolerance, evade therapies through adaptive mechanisms such as quiescence, metabolic reprogramming, epigenetic modifications, and signaling pathway activation. These cells, pivotal in mediating therapeutic resistance, dynamically evolve from reversible tolerance to stable resistance, fueling disease relapse. This review elucidates the clinical significance of MRD and DTP cells, detailing their biological characteristics, detection technologies, and formation mechanisms. We highlight therapeutic strategies targeting DTP cells, including pathway inhibitors, epigenetic modulators, and autophagy blockers, to reverse MRD and prevent recurrence. Challenges in translating these approaches to clinical practice, such as DTP heterogeneity and biomarker development, are addressed alongside emerging technologies like single-cell omics and AI-driven analytics. By integrating mechanistic insights with innovative detection and therapeutic strategies, targeting DTP cells within MRD holds transformative potential to enhance long-term cancer outcomes.
SN - 2731-4529
ER -