Epithelial-mesenchymal transition and drug resistance: role, molecular mechanisms, and therapeutic strategies

Chemotherapy is an important therapeutic option for most cancer patients; however, one major obstacle is the occurrence of drug resistance which usually leads to failure of the chemotherapy. Emerging evidence suggests that there are intricate links between epithelial-mesenchymal transition (EMT)-type cells and drug resistance in tumors. The process of drug resistance can be regulated by a diverse array of cytokines and growth factors, higher apoptotic threshold, aerobic glycolysis, regions of hypoxia, and elevated activity of drug efflux transporters. Moreover, recent reports have indicated that the emergence of drug resistance may occur as a result of EMT. In this regard, most drug-resistant cancers contain a subpopulation of cells with stem-like and mesenchymal features that are resistant to chemotherapy. In this review, we will explain potential mechanisms for the association between EMT induction and the emergence of drug resistance, and discuss new approaches and drugs for the clinical management of drug-resistant cancer induced by EMT.