encorafenib + buparlisib

**Encorafenib + buparlisib** is an experimental combination of two small molecule targeted therapies: encorafenib, a selective BRAF kinase inhibitor, and buparlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor. Both drugs target key oncogenic signaling pathways frequently dysregulated in cancers: BRAF mutations activate the MAPK/ERK pathway, while PI3K pathway alterations confer growth and survival advantages. This combination was explored for BRAF^V600^-mutant cancers, including melanoma, to concurrently inhibit BRAF-driven tumor proliferation (via encorafenib) and PI3K-mediated resistance pathways (via buparlisib). Development was halted early due to significant drug–drug interactions and lack of efficacy in trials[1].