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Determining PARP Inhibition as a Treatment Strategy in Melanoma Based on Homologous Recombination Deficiency–Related Loss of Heterozygosity

Journal of the National Comprehensive Cancer Network Manuscript
Authors Alice Zhou, Omar Butt, Michael Ansstas, Elizabeth Mauer, Karam Khaddour, and George Ansstas

There is a lack of effective treatments for immunotherapy-refectory melanoma. Although PARP inhibitors (PARPi) are an effective treatment strategy in cancers with homologous recombination deficiency (HRD), determining HRD status is challenging in melanoma. Here, we chart the longitudinal relationship between PARPi response and HRD scores derived from genome-wide loss of heterozygosity (LOH) in 4 patients with metastatic melanoma. When next examining 933 melanoma cases, using an updated threshold, we observed HRD-related LOH (HRD-LOH) in nearly one-third of all cases compared with <10% using traditional gene panels. Taken together, HRD-LOH in refractory melanoma is both a common occurrence and a potential biomarker for response to PARPi.