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- Title
Evaluating the Effect of Lenvatinib on Sorafenib-Resistant Hepatocellular Carcinoma Cells.
- Authors
Shi, Tingting; Iwama, Hisakazu; Fujita, Koji; Kobara, Hideki; Nishiyama, Noriko; Fujihara, Shintaro; Goda, Yasuhiro; Yoneyama, Hirohito; Morishita, Asahiro; Tani, Joji; Yamada, Mari; Nakahara, Mai; Takuma, Kei; Masaki, Tsutomu
- Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Sorafenib has been used as a first-line systemic treatment for over a decade. However, resistance to sorafenib limits patient response and presents a major hurdle during HCC treatment. Lenvatinib has been approved as a first-line systemic treatment for advanced HCC and is the first agent to achieve non-inferiority against sorafenib. Therefore, in the present study, we evaluated the inhibition efficacy of lenvatinib in sorafenib-resistant HCC cells. Only a few studies have been conducted on this topic. Two human HCC cell lines, Huh-7 and Hep-3B, were used to establish sorafenib resistance, and in vitro and in vivo studies were employed. Lenvatinib suppressed sorafenib-resistant HCC cell proliferation mainly by inducing G1 cell cycle arrest through ERK signaling. Hep-3B sorafenib-resistant cells showed partial cross-resistance to lenvatinib, possibly due to the contribution of poor autophagic responsiveness. Overall, the findings suggest that the underlying mechanism of lenvatinib in overcoming sorafenib resistance in HCC involves FGFR4-ERK signaling. Lenvatinib may be a suitable second-line therapy for unresectable HCC patients who have developed sorafenib resistance and express FGFR4.
- Subjects
HEPATOCELLULAR carcinoma; DRUG resistance in cancer cells; CELL proliferation; SORAFENIB; CELL lines; IN vivo studies
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 23, p13071
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms222313071