Combinatorial therapy regimens targeting preclinical models of melanoma resistant to immune checkpoint blockade.

ABSTRACT: Few effective therapeutic options exist after progression on immune checkpoint blockade (ICB) for melanoma. Here, we utilized a platform incorporating transcriptomic profiling, high-throughput drug screening, and murine models to demonstrate the preclinical efficacy of several combinatorial regimens against ICB-resistant melanoma. Transcriptomic analysis of ICB-resistant melanomas demonstrated activation of several targetable pathways. High-throughput drug screening targeting these pathways identified several effective combinations in ICB-resistant patient-derived xenograft models. The combination of cobimetinib and regorafenib (termed Cobi+Reg) emerged as a particularly promising regimen, with efficacy against distinct molecular melanoma subtypes and after progression on ICB in immunocomp

SUBMITTER: Khan I 

PROVIDER: S-EPMC12490269 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature