Targeted therapies and PARPi therapy response following ICI therapy failure in advanced melanoma: a case series.

ABSTRACT: Poly (ADP-ribose) polymerase inhibitors (PARPi) have shown efficacy in treating cancers with homologous recombination deficiency (HRD), including subsets of melanoma. However, the potential synergy between PARPi and standard melanoma therapies remains understudied. Here, we report two cases of advanced metastatic melanoma refractory to standard-of-care treatment that demonstrated durable partial responses following the addition of PARPi in combination with immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors. Both patients exhibited homologous recombination repair (HRR) pathway mutations and tolerated the combinatory regimens well, achieving progression-free survival of more than 11 months. Mechanistically, PARPi may enhance immunogenicity to ICI therapy via activation of the cyclic

SUBMITTER: Nassief G 

PROVIDER: S-EPMC12694906 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature