EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets

Cancer continues to be a primary cause of death, resulting in substantial mortality and illness globally. It remains a significant global health issue, greatly affecting morbidity and mortality across the world. Therapeutic resistance poses a major challenge to cancer treatments, acting as a significant barrier to the effectiveness of both standard and targeted therapies. This resistance develops through various mechanisms that allow tumor cells to adapt to and escape the damaging effects of chemotherapy, radiation, and targeted therapies. Ultimately, this leads to disease recurrence and progression. This review examines the dual roles of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) in promoting chemoresistance and metastasis. EMT is a dynamic and reversible biological process in which epithelial cells acquire mesenchymal characteristics, increasing their invasiveness and resistance to programmed cell death. CSCs are a subset of cancer cells with the ability to self-renew and play a crucial role in tumor relapse and resistance to treatment. EMT and CSCs are closely interconnected, collaboratively enhancing cancer cell plasticity, metastatic ability, and treatment resistance. The initiation of EMT in cancer cells can generate a CSC-like population, which promotes tumor recurrence and spread. This interaction highlights the importance of targeting both EMT and CSC pathways to develop more effective treatment strategies that address treatment resistance and prevent metastasis. Promising approaches include using natural substances, small molecules, and nanotechnology to block critical signaling pathways and interfere with resistance mechanisms. A more thorough understanding of the molecular factors underlying EMT and CSC plasticity is crucial for crafting personalized treatments that target tumor heterogeneity and improve clinical outcomes.