New insights into sorafenib resistance in hepatocellular carcinoma: Responsible mechanisms and promising strategies

Biochim Biophys Acta Rev Cancer. 2017 Dec;1868(2):564-570. doi: 10.1016/j.bbcan.2017.10.002. Epub 2017 Oct 17.

Abstract

It is disappointing that only a few patients with hepatocellular carcinoma (HCC) obtain a significant survival benefit from the sorafenib treatment, which is currently regarded as a first-line chemotherapeutic therapy in patients with advanced HCC. Most patients are highly refractory to this therapy. Therefore, it is necessary to identify resistant factors and explore potential protocols that can be used to overcome the resistance or substitute sorafenib once the resistance is formed. In fact, a growing body of studies has been focusing on the resistance mechanisms or the method to overcome it. The limitation of sorafenib efficacy has been partially but not fully elucidated. Moreover, some protocols have shown encouraging outcomes but still need to be further verified in clinical trials. In this review, we summarize the recent findings on the potential mechanisms that contribute to sorafenib resistance and discuss strategies that can be used to improve the treatment outcome.

Keywords: Drug resistance; Liver cancer; Molecular targeted therapy; Sorafenib.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Autophagy
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / physiology
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • MicroRNAs / physiology
  • Neoplastic Stem Cells / physiology
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Protein Kinase Inhibitors / therapeutic use*
  • Sorafenib

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • PDCD1 protein, human
  • Phenylurea Compounds
  • Programmed Cell Death 1 Receptor
  • Protein Kinase Inhibitors
  • Niacinamide
  • Sorafenib
  • ErbB Receptors