tipifarnib + alpelisib

Tipifarnib + alpelisib is an investigational combination therapy comprised of two oral small molecule inhibitors: **tipifarnib**, a farnesyltransferase inhibitor that targets oncogenic effector proteins such as HRAS and RHEB, and **alpelisib**, a selective inhibitor of the p110α catalytic subunit of **phosphoinositide 3-kinase alpha (PI3Kα)**. This combination is being developed primarily for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) characterized by dysregulation of **PIK3CA** and/or **HRAS** signaling. Mechanistically, tipifarnib blocks feedback reactivation of MAPK and mTOR pathways (via inhibition of HRAS/RHEB farnesylation) that normally occurs after PI3K inhibition with alpelisib, resulting in deeper and sustained inhibition of tumor signaling, cell cycle arrest, and induction of apoptosis. This combinatorial pathway blockade is predicted to overcome resistance to PI3Kα monotherapy and achieve synergistic antitumor effects in HNSCC models with PIK3CA mutations/amplification or HRAS elevation[1][2][3][4][5][6].

Brand names

None known for the combinationtipifarnib (brand name not established; commonly referred by generic or investigational name)alpelisib (branded as Piqray, but for the combination, the canonical name is used)

Other names

tipifarnib + alpelisib