Cancer Management and Research

Targeting Cancer Stem Cells to Overcome Therapy Resistance: Mechanisms, Biomarkers, and Clinical Translation

Cancer stem cells (CSCs) are a therapy-resistant subpopulation that drives tumor initiation, progression, metastasis, and recurrence. Their capacity for self-renewal, plasticity, and adaptation underpins resistance to chemotherapy, radiotherapy, and immunotherapy, making them a central obstacle to long-term therapeutic success. Eradicating CSCs is thus recognized as a critical goal in improving long-term patient survival.

However, CSC research and targeted therapy face numerous challenges. Currently, there is a lack of universally applicable CSC-specific biomarkers, making it difficult to precisely target CSCs without damaging normal stem cells. Furthermore, CSCs continuously interact with the tumor microenvironment, including hypoxic homeostasis, matrix support, and immune regulation; these external conditions further enhance CSC survival and drug resistance. Recent advances in single-cell omics, spatial omics, and artificial intelligence technologies have provided new tools for revealing the heterogeneity, metabolic characteristics, and regulatory networks of CSCs. Based on these technological innovations, new strategies such as metabolic inhibition, synthetic biology intervention, and immunotherapy are being studied to target CSCs, with the potential to overcome CSC-mediated therapeutic resistance.

This Article Collection aims to gather the latest research progress in the field of cancer stem cells and to facilitate exchange and discussion on key issues such as drug resistance mechanisms, biomarker discovery, and clinical translation. Selected high-quality contributions from the 2026 International Conference on New Models for Cancer Prevention and Treatment (NMCPT 2026, http://www.nmcpt.com/), together with externally submitted manuscripts, will be included. Both original research articles and authoritative reviews are welcome.

Topics of interest include, but are not limited to:
• Molecular Mechanisms & Biomarkers: Intrinsic and microenvironment-mediated resistance pathways; discovery and validation of CSC-associated biomarkers for diagnosis, prognosis, and treatment stratification.
• Tumor Ecosystem: The role of the tumor microenvironment (immune, stromal, metabolic) in sustaining CSCs and fostering therapeutic escape.
• Innovative Therapeutics: Novel strategies targeting CSC vulnerabilities, including small molecules, immunotherapies, epigenetic modulators, and rational combination therapies.
• Translational & Clinical Research: Preclinical validation in advanced models (e.g., patient-derived organoids, in vivo models); pilot and early-phase clinical trials of CSC-targeting agents; studies on minimal residual disease and recurrence.

Submitting authors are eligible for a 10% discount on the Article Publishing Charge. To apply this discount, enter the code B4C3A when prompted during submission.