Topic: Extracellular Vesicles in Cancer Therapy Resistance: Metabolic Reprogramming, Tumor Microenvironment Crosstalk and Precision Therapeutics

Therapy resistance remains the main barrier to durable responses in cancer, limiting the efficacy of chemotherapy, radiotherapy, targeted agents and immunotherapy. Extracellular vesicles (EVs) have emerged as key mediators of this process. By transferring proteins, nucleic acids, lipids and metabolites between cells, EVs allow resistant tumor cells to spread their phenotype to sensitive neighbors and to reshape the tumor microenvironment (TME) in ways that support survival under therapeutic pressure.

Growing evidence links EV signaling to metabolic reprogramming, a hallmark of resistant tumors. EVs deliver enzymes, transporters and regulatory RNAs that rewire glycolysis, mitochondrial respiration, and amino acid and lipid metabolism, while vesicles from cancer-associated fibroblasts, immune and endothelial cells supply nutrients and signals that protect tumor cells from drug-induced stress. This crosstalk also drives immunosuppression, drug sequestration and stem-like cell states.

The same EV cargo offers new opportunities for precision oncology. Circulating EVs are promising liquid biopsy biomarkers for predicting and monitoring treatment response, and engineered EVs are being developed as therapeutic carriers and as tools to disrupt resistance-promoting communication.

This Special Issue welcomes original research and review articles on how EVs drive therapy resistance and how this knowledge can be translated into clinical benefit. Topics include, but are not limited to:

● EV-mediated transfer of drug resistance;

● EVs and metabolic reprogramming in resistant cancers;

● EV crosstalk among tumor, stromal and immune cells;

● EVs in resistance to immunotherapy;

● EV-based biomarkers of therapy response and relapse;

● Engineered EVs and EV-targeting strategies to overcome resistance;

● Advances in EV isolation, characterization and single-vesicle analysis.