Dr. Kaseb on Research With Targeted Therapy in HCC

Ahmed O. Kaseb, MD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses research with targeted therapy in hepatocellular carcinoma (HCC).

FGF inhibitors and TGF-β inhibitors are being evaluated, says Kaseb. Notably, tumors with advanced cirrhosis tend to have molecular alterations in TGF-β. Additionally, some studies have looked at RAS alterations. However, the overall percentage of patients with potentially targetable alterations is less than 5%, says Kaseb. One Asian study evaluated the use of RAS inhibitors in only 1% of the 2000 patients screened. TKIs, however, could have greater utility because they cause a downstream effect that could augment the effect of immunotherapy.

If TGF-β or STAT3 inhibitors, which are associated with immune suppression, can also be combined with immunotherapy, it could lead to greater utility in the field, explains Kaseb. At The University of Texas MD Anderson Cancer Center, investigators are planning a study that will evaluate STAT3 inhibitors plus checkpoint inhibitors, which could also help overcome acquired resistance mechanisms to immunotherapy, concludes Kaseb.