A pharmaceutical composition comprising sorafenib and GW5074. Said combination therapy inhibits cancer cell growth via c-Raf-PP2A-DAPK signaling transduction pathway in either in vitro or in preclinical animal model for orthotopic spontaneous kidney cancer which simulates clinical symptoms. Formation of the bond between c-Raf and GW5074 leads to conformational change which consequently increases the affinity between sorafenib and c-Raf. Binding with the specific drug target facilitates serine 308 dephosphorylation of DAPK by PP2A and induces necrosis in cancer cells. Serine 308 of DAPK protein may also be used as a biomarker for drug screening. This study provides a novel pharmaceutical composition comprising sorafenib and GW5074, a protein complex target consisting of c-Raf and DAPK for drug designing, as well as biomarkers including c-Raf protein, DAPK protein and phosphorylation status of DAPK for drug screening.
