In this study, we characterized three BRAFV600E-mutant PDTX mouse models with disparate responses to dual dabrafenib and trametinib SOC, and discovered that palbociclib sensitized tumors to SOC by eliciting tumor regressions and durable responses in BRAF/MEK inhibitor responsive and resistant tumors when used as an upfront treatment. Here, BRAF is linked to neoplasm.