Multiplex in vivo RNAi screening instructs combination therapies to increase the therapeutic efficacy of the multikinase inhibitor sorafenib

Hepatocellular carcinoma represents the third common cause of cancer death and the incidence is steadily increasing. Standard treatments are limited due to frequent tumor recurrence and a poor responsiveness to conventional chemotherapy. The approval of sorafenib, a small multikinase inhibitor as the first active systemic treatment against HCC, increases survival of HCC patients by less than 3 months. Thus, there is a strong need to understand the molecular mechanisms of sorafenib sensitivity and resistance in order to instruct sorafenib basedcombination therapies with higher therapeutic efficacy. Activation of…