REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1634413
This article is part of the Research TopicMulti-omics Application in Exploring Potential Biomarkers Targeting Resistance of Anti-Cancer Drugs, Volume IIView all 8 articles
Multi-omics Dissection of Tumor Microenvironment-Mediated Drug Resistance: Mechanisms and Therapeutic Reprogramming
Provisionally accepted
- Fudan University, Shanghai, China
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Tumor drug resistance represents a major challenge in contemporary cancer therapeutics, significantly compromising the clinical efficacy of chemotherapy, targeted therapy, and immunotherapy. While existing research has elucidated the critical role of tumor cell-intrinsic mechanisms in drug resistance-including genomic instability, persistent activation of signaling pathways and aberrant epigenetic modifications-emerging evidence highlights the crucial involvement of dynamic remodeling within the tumor microenvironment(TME) in driving therapeutic resistance. The TME fosters drug resistance through dynamic remodeling, creating hypoxic conditions, immunosuppressive networks, and metabolic stress, which collectively impair treatment response and promote therapeutic escape. Advances in multi-omics technologies, now enable a comprehensive, multi-dimensional analysis of these interactions, integrating genomic, epigenomic, transcriptomic, proteomic, and metabolomic data to uncover critical molecular networks and vulnerabilities. In this review, we explore the key mechanisms by which the TME influences drug resistance, discuss how multi-omics approaches enhance our understanding of these processes and evaluate emerging therapeutic strategies aimed at reprogramming the TME to overcome resistance.
Keywords: Tumor Microenvironment, Drug Resistance, multi-omics, therapeutic strategies, Drug delivery, Immune Evasion
Received: 24 May 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 Fanghua, Yuandong, Gaigai, Junjun and Hua. 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: Keqin Hua, Fudan University, Shanghai, China
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