INHIBITION OF LIGAND-DEPENDENT BMP SIGNALING BLUNTS MELANOMA GROWTH

Treatments for advanced melanoma have markedly improved, but a significant proportion of patients still receive little to no survival benefit with standard-of-care therapies due to resistance and relapse1-5. The discovery and development of novel targets and therapies are needed to continue to improve patient outcomes in advanced melanoma. The identification of ligand-dependent BMP signaling that inhibits differentiation and promotes survival of melanoma cells suggests it is a potential therapeutic target that could complement current therapies6. Expression of the BMP ligand GDF6 (a.k.a BMP13) is responsible for this activity, and its expression is correlated with poor outcomes for melanoma patients. Here, we describe a novel monoclonal antibody targeting GDF6 that causes melanoma cell differentiation and death and blunts tumor growth in vivo. Together, these results indicate BMP-directed therapy has significant potential as a novel therapy for patients with advanced melanoma.