article · Clinical and Translational Discovery
The epithelial-mesenchymal transition, or EMT, is a key biological process that drives cancer metastasis and presents a major barrier to effective treatment. During EMT, cancer cells gain mobility, invade distant organs, penetrate blood vessels, and form secondary tumours through a reverse transition. This process is governed by a complex network of transcription factors, signalling pathways, metabolic shifts, non-coding RNAs, epigenetic modifications, exosomes, and the tumour microenvironment. Beyond facilitating cell spread, EMT plays a substantial role in tumour dormancy, cellular senescence, the emergence of cancer stem cells, and resistance to standard therapies. An analysis of current EMT-focused clinical trials highlights notable breakthroughs alongside persistent hurdles, indicating that targeting these cellular mechanisms remains a vital focus for improving cancer management and treatment strategies.
Metastasis and drug resistance are the primary causes of treatment failure in cancer care. Understanding the molecular switches that allow cancer cells to move, hide, and resist therapy is crucial for creating treatments that stop cancer from spreading or returning, potentially transforming long-term patient outcomes across multiple cancer types.
The findings inform pharmaceutical and biotechnology developers targeting metastasis and drug resistance. Potential applications include drug discovery programmes aimed at EMT signalling pathways, cancer stem cells, and reversal mechanisms. Given that the work discusses ongoing clinical trials alongside persistent developmental challenges, resulting therapies appear to range from early-stage translation to mid-stage clinical evaluation.
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Abstract The epithelial–mesenchymal transition (EMT) represents a pivotal frontier in oncology, playing a central role in the metastatic cascade of cancer—a leading global health challenge. This comprehensive review delves into the complexities of EMT, a process where cancer cells gain exceptional mobility, facilitating their invasion into distant organs and the establishment of secondary malignancies. We thoroughly examine the myriad of factors influencing EMT, encompassing transcription factors, signalling pathways, metabolic alterations, microRNAs, long non‐coding RNAs, epigenetic changes, exosomal interactions and the intricate dynamics of the tumour microenvironment. Particularly, the review emphasises the advanced stages of EMT, crucial for the development of highly aggressive cancer phenotypes. During this phase, cancer cells penetrate the vascular barrier and exploit the bloodstream to propagate life‐threatening metastases through the mesenchymal–epithelial transition. We also explore EMT's significant role in fostering tumour dormancy, senescence, the emergence of cancer stem cells and the formidable challenge of therapeutic resistance. Our review transcends a mere inventory of EMT‐inducing elements; it critically assesses the current state of EMT‐focused clinical trials, revealing both the hurdles and significant breakthroughs. Highlighting the potential of EMT research, we project its transformative impact on the future of cancer therapy. This exploration is aimed at paving the way towards an era of effectively managing this relentless disease, positioning EMT at the forefront of innovative cancer research strategies.
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DOI: 10.1002/ctd2.260
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