Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma

Title:Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma

Volume: 17 Issue: 8

Author(s): Nabiel Mir, Aparna Jayachandran, Bijay Dhungel, Ritu Shrestha and Jason C. Steel*

Affiliation:

• The University of Queensland, School of Medicine, Gallipoli Medical Research Institute, Lower Lobby Level, Administration Building, Greenslopes Private Hospital, Greenslopes, Qld 4120,Australia

Keywords: HCC, sorafenib, EMT, drug resistance, cancer stem cells, cancer.

Abstract: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and its incidence is steadily rising. Currently, sorafenib remains the only approved standard treatment for patients with advanced HCC, as it has proven to increase survival in these patients. However, clinical and preclinical observations indicate that sorafenib treatment may have limited efficacy due to tumor progression from the rapid development of acquired resistance. Elucidation of the underlying mechanisms of evasive resistance to sorafenib is a major challenge in HCC research. In recent years, the role of epithelial-to-mesenchymal transition (EMT) in the advancement of HCC and development of drug resistance has gained increasing attention. EMT is a developmental multistep molecular and cellular reprogramming process that is hijacked by cancer cells to enable aggressiveness. In this review, we provide an overview of the currently available preclinical studies on the EMT mechanisms underlying resistance to sorafenib treatment. Recent studies report enrichment of cancer stem cells (CSCs) after sorafenib treatment. Interestingly, EMT process has been implicated in the generation of CSCs associated with therapy resistance. We discuss how combination of sorafenib with EMT inhibitors could enhance the clinical response to sorafenib, resulting in longer duration of responses, than observed with sorafenib monotherapy. In particular, we discuss how these new insights may facilitate rational development of combination therapies in the future to impact survival of patients with advanced HCC.

Cite this article as:

Mir Nabiel , Jayachandran Aparna, Dhungel Bijay , Shrestha Ritu and Steel C. Jason *, Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma, Current Cancer Drug Targets 2017; 17 (8) . https://dx.doi.org/10.2174/1568009617666170427104356