Research on Tumor Drug Resistance Mediated by Epithelial-mesenchymal Transition

Abstract

Epithelial-mesenchymal transition (EMT) is a key biological process driving tumor invasion and metastasis, and its activation is widely regarded as one of the core mechanisms leading to tumor resistance to multiple therapeutic approaches. Current research indicates that EMT mediates drug resistance through multiple pathways, such as conferring stem cell-like properties to cancer cells, miRNA delivery via exosomes, and promoting drug efflux. The underlying mechanisms of related signaling pathways and key transcription factors are being intensively investigated. However, effectively translating the basic research findings targeting EMT to overcome drug resistance into clinical applications still faces significant challenges. This article systematically reviews the core molecular mechanisms by which EMT mediates tumor drug resistance, with a focus on how EMT confers drug-resistant phenotypes to cancer cells by regulating tumor stem cell characteristics and drug pharmacokinetics. It also reviews experimental strategies targeting key EMT molecules to reverse drug resistance and their preclinical/clinical research evidence. This review provides a theoretical framework for a deeper understanding of the role of EMT in tumor drug resistance and lays the foundation for developing novel combination treatment regimens based on EMT intervention. Future research urgently needs to explore more selective EMT-targeting strategies, identify reliable predictive biomarkers, and optimize their synergistic effects with traditional radiotherapy, chemotherapy, and immunotherapy to ultimately improve the prognosis of patients with refractory tumors.