Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy

Biochim Biophys Acta Rev Cancer. 2020 Aug;1874(1):188391. doi: 10.1016/j.bbcan.2020.188391. Epub 2020 Jul 10.

Abstract

Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), is an emerging first-line therapy for hepatocellular carcinoma (HCC). Its application has changed the status of sorafenib as the only first-line TKI treatment for HCC for more than a decade. Evidence has shown that lenvatinib possesses antitumor proliferation and immunomodulatory activity in preclinical studies. In comparison, lenvatinib was non-inferior to sorafenib in overall survival (OS), and even shows superiority with regard to all the secondary efficacy endpoints. Immune-checkpoint inhibitors(ICIs)are now being incorporated into HCC treatment. Positive outcomes have been achieved in the combination of lenvatinib plus ICIs, bringing broader prospects for HCC. This review presents an overview on the therapeutic mechanisms and clinical efficacy of lenvatinib in HCC, and we discuss the future perspectives of lenvatinib in HCC management with focus on biomarker-guided precision medicine.

Keywords: Clinical efficacy; HCC; Lenvatinib; Molecular mechanisms; Precision medicine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Humans
  • Immunomodulation
  • Immunotherapy
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • lenvatinib