Cancer

Cell culture and mouse studies suggest inhibiting RAF1 could help treat KRAS-driven lung cancer. In tumor cells from two patient-derived xenograft (PDX) mouse models of KRAS-driven lung cancer, shRNA targeting RAF1 encoded in a lentiviral vector decreased proliferation compared with scrambled shRNA. Also in the PDX model, tumor-specific knockdown of RAF1 decreased tumor growth. In a mouse model of KRAS-driven lung cancer, systemic knockout of RAF1 decreased tumor volume and increased tumor cell apoptosis and survival compared with normal RAF1 expression. Next steps could include identifying and testing RAF1 inhibitors in models of KRAS-driven lung cancer.

Novartis AG has RAF265, a small molecule inhibitor of the Raf kinases, in Phase II testing to treat melanoma and Phase I testing to treat advanced solid tumors...