Therapeutic Exosomes for Rare Cancers: Advances and Clinical Translation

Rare cancers collectively account for a proportion of cancer-related morbidity and mortality, and patients face significant challenges, including delayed diagnosis, lack of targeted therapies, and poor clinical outcomes. Exosome-based therapies have emerged as promising tools to address these unmet needs. Exosomes, naturally secreted extracellular vesicles, are increasingly engineered as nanocarriers for the targeted delivery of chemotherapeutics, nucleic acids, and immune modulators. Their ability to modulate the tumor microenvironment, influence immune responses, and overcome drug resistance makes them especially attractive. In rare cancers, preliminary studies have demonstrated the utility of exosomes in improving tumor specificity, enhancing payload stability, and reducing systemic toxicity. Moreover, exosomes derived from tumor or immune cells can influence immune evasion, angiogenesis, and stromal remodeling, key processes in cancer progression. Despite this potential, the clinical application of exosome-based therapies in rare cancers remains underexplored. This review critically evaluates the limited but emerging body of evidence supporting exosome-based interventions in rare malignancies. By highlighting their therapeutic promise, we aim to understand exosome-driven strategies as personalized, effective, and accessible solutions for patients with rare cancers.