Abstract 896: Adjutant Therapeutic Strategy for Sorafenib-Resistant Hepatocellular Carcinoma

Abstract Purpose: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the leading cause of cancer mortality worldwide. To date, Sorafenib remains the standard of care for advanced HCCs not amenable to curative therapies such as surgery or local ablation. Unfortunately, clinical efficacy of Sorafenib remains marginal as most HCC patients receiving Sorafenib treatment develop Sorafenib resistance. The recently approved regorafenib is the only rescue therapy for patients who fail Sorafenib treatment. However, the effect of regorafenib is also far from satisfactory. Therefore, new strategies to overcome sorefenib resistance are critically warranted. Recently, one FDA-approved drug, here we tentatively named as “FA”, was shown to suppress different cancer malignancy by various mechanisms including inhibiting the development of drug resistance in cancer. These findings provide a rationale for combination treatment of this FA drug with Sorafenib in Sorafenib-resistant HCC. Results: Two Sorafenib-resistant HCC cell lines of Hep3B and HepG2215 were established. The Sorafenib resistance characteristics of the HCC cells were further verified by western blotting assay detecting protein tyrosine phosphorylation. We also demonstarted the resistant HCC cells expressed stemness-related genes and showed high ability of cell migration and metastasis. Combination use of FA drug and Sorafenib significantly suppressed the cell viability as well as the stemness-related properties of Sorafenib-resistant HCC cells, including stemness-related gene/protein expression, secondary sphere formation, and the cell migration. Conclusion: Combination use of FA drug and Sorafenib would be a potential therapeutic strategy for Sorafenib-resistant HCC treatment. Citation Format: Syue-Wei Peng, Yi-Heng Lin, Ming-Hao Teng, Hung-Cheng Lai, Te-Sheng Chang, Yen-Hua Huang. Adjutant therapeutic strategy for sorafenib-resistant hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 896.