Melanoma is the most aggressive skin cancer, with a 50% five-year mortality in metastatic or unresectable cases. Non-invasive biomarkers are crucial for guiding treatment. MicroRNAs (miRNAs), especially those encapsulated in extracellular vesicles (EVs), are stable in plasma and hold promise as biomarkers. This study analyzed EV-associated miRNAs (EV-miRNAs) from 50 blood samples of 18 stage III-IV melanoma patients treated with anti-CTLA-4 immunotherapy and a DNA hypomethylating agent. Samples were collected at baseline, week 4, and week 12. Patients were classified as responders (R) or non-responders (NR). A baseline signature of four EV-miRNAs predicted primary resistance. Treatment altered 15 EV-miRNAs at week 4 and 51 at week 12; nine were consistently modulated. At week 12, 27 EV-miRNAs differed between NR and R, with miR-1203 and miR-566-3p up-regulated in NR, linked to resistance and poor survival. These results highlight EV-miRNAs as non-invasive biomarkers for predicting and monitoring therapy response. This study aimed to develop easy and minimally invasive methods to predict and monitor how patients with advanced melanoma respond to immunotherapy and epigenetic treatments. Melanoma is a serious and often deadly skin cancer, and better tools are needed to guide treatment decisions. The researchers studied microRNAs, small molecules found in particles in the blood, from melanoma patients before and during treatment. They found specific microRNAs that can predict which patients may not respond to therapy. These blood-based microRNA biomarkers could help physicians to personalize the treatments, leading to more effective care and better outcomes for patients in the future. Splendiani, Besharat, Sabato et al., evaluate circulating extracellular vesicle microRNAs before and during combined therapy in metastatic melanoma. They identify four and two EV-miRNA signatures as markers of primary and acquired resistance, providing key insights for precision oncology.
Splendiani et al. (Thu,) studied this question.