Synergistic Targeting of Hepatocellular Carcinoma via Novel Regorafenib Combinations with Diosmin, Sulfasalazine, or Rosuvastatin.

Hepatocellular carcinoma (HCC), the most common liver cancer, has limited treatment options. The author investigated novel combinations of regorafenib (Reg) with diosmin (Dio), sulfasalazine (SZZ), or rosuvastatin (Ros) to enhance anti-HCC efficacy. Each agent potentiated Reg activity via distinct pathway modulation: Reg/Dio inhibited Akt/m-TOR and RAF/ERK; Reg/SZZ suppressed Akt/m-TOR and NF-κB; and Reg/Ros suppressed JAK/STAT3 and RAF/ERK. These findings demonstrate synergistic potential by combining Reg with drugs possessing complementary anti-inflammatory, cholesterol-lowering, or cytotoxic activities, offering promising multi-targeted therapeutic strategies for HCC.