CS-1008 + sorafenib

**CS-1008 + sorafenib** is an investigational combination therapy for cancer, primarily hepatocellular carcinoma (HCC). CS-1008 (tigatuzumab) is a humanized monoclonal IgG1 antibody that agonizes **death receptor 5 (TNFRSF10B/DR5)**, promoting apoptosis in cancer cells. Sorafenib is a multikinase inhibitor approved for HCC and other malignancies. When used together, sorafenib enhances CS-1008-induced apoptosis in resistant HCC cells by downregulating phosphorylated STAT3 protein (through SHP-1-dependent inactivation), subsequently reducing expression of anti-apoptotic proteins (Mcl-1, survivin, cyclin D1), and activating the caspase cascade (caspase-8, caspase-9, caspase-3), culminating in PARP cleavage and intrinsic apoptosis. The combination overcomes resistance to individual agents and results in greater anti-tumor activity in preclinical models.

Other names

CS-1008CS1008CS 1008tigatuzumabsorafenib