Decoding EMT through liquid biopsy: A path to early detection and targeted therapy

Epithelial-mesenchymal transition (EMT) is a key biological process that enables cancer cells to acquire invasive, migratory, and therapy-resistant properties, driving metastasis and poor clinical outcomes. Traditional tissue biopsies, while informative, provide only static and localized snapshots of tumors, limiting their ability to capture dynamic changes like EMT. Liquid biopsy has emerged as a powerful, minimally invasive tool to monitor tumor evolution in real time by analyzing circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) from body fluids. This review highlights the molecular mechanisms that govern EMT, including transcriptional, signaling, and epigenetic regulation, and discusses how EMT-associated alterations can be detected through liquid biopsy. We explore the clinical applications of EMT monitoring via liquid biopsy for early detection of metastasis, prognostic assessment, therapy selection, and monitoring minimal residual disease (MRD). Despite current challenges such as the biological complexity of EMT, detection sensitivity, and the need for standardization, technological advances and emerging computational tools are paving the way for the integration of liquid biopsy into precision oncology. Understanding and decoding EMT through liquid biopsy represents a promising frontier for improving cancer diagnosis, prognosis, and therapeutic strategies, offering hope for more personalized and effective cancer management in the future.