EMT and cancer: what clinicians should know

Abstract

Cell plasticity is a crucial trait for cancer progression towards metastasis and treatment resistance. Research efforts from the past 20–30 years have revealed that the dynamic flux of the epithelial–mesenchymal transition (EMT) programme is one of the major underlying processes enabling cancer cell plasticity and greatly facilitates these major causes of cancer mortality. The spectrum of evidence ranges from extensive data from cell line and animal model studies across multiple cancer types through a rapidly expanding body of work demonstrating associations between EMT biomarkers and disease progression and mortality in patients. EMT is also implicated in resistance to most of the major treatment modalities, yet our efforts to harness this knowledge to improve therapeutic outcomes are currently in their early stages. In this Review, we describe clinical evidence supporting a role of EMT and the associated epithelial–mesenchymal plasticity in various stages of cancer in patients and discuss the subsequent clinical opportunities and challenges associated with attempts to implement this knowledge as novel therapies or clinical management approaches. Despite several decades of research that has revealed roles in the development and progression of many solid tumours, clinical translation of research targeting epithelial–mesenchymal transition (EMT) has thus far been limited. In this Review, the authors provide a summary of the role of EMT in cancer development and progression in the context of this lack of clinical translation, summarize the current status of direct or indirect EMT-modulating agents in clinical development, and highlight the major barriers to the development of EMT-related clinical interventions.