Abstract 5086: The side effects of sorafenib in treating hepatocellular carcinoma.

Sorafenib, a tyrosine kinase inhibitor of VEGFR and B-Raf, is a standard treatment for advanced hepatocellular carcinoma (HCC). However, there are several clinical observations showing discontinuous sorafenib treatment associated with more metastasis or rapid relapse. We tested effect of sorafenib on tumor growth and metastasis in different dosing and schedules in liver cancer allograft or xenograft models. The results showed a lower dose sorafenib treatment will induce more intrahepatic or lung metastasis while the primary tumor growth is still inhibited in HCC with a higher expression of HTATIP2 but not in HCC with a lower expression of HTATIP2. Further studies showed sorafenib decreased HTATIP2 expression only in HCC with a higher expression of HTATIP2. The clinical data also supported the patients with lower HTATIP2 expression in tumor benefit from sorafenib treatment while patients with a higher HTATIP2 expression in tumor did not. We also observed the effect of sorafenib on host (mouse) immunity after we found pre-treatment by sorafenib before implantation of tumor resulted in more lung metastasis. We found interleukin 12 (IL12) was significantly inhibited by sorafenib, which is responsible for more lung metastasis. In conclusion, our study showed the side effect of sorafenib may promote tumor progression if sorafenib treatment is stopped or not given in a full dose. These findings may help to improve the efficacy of sorafenib by overcoming its side effects. Citation Format: Hui-Chuan Sun, Wei Zhang, Xiao-Dong Zhu, Lu Lu, Qiang-Bo Zhang, Zhao-You Tang. The side effects of sorafenib in treating hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5086. doi:10.1158/1538-7445.AM2013-5086 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.