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

Mir, Nabiel, Jayachandran, Aparna, Dhungel, Bijay, Shrestha, Ritu and Steel, Jason C. (2017) Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma. Current Cancer Drug Targets, 17 8: 698-706. doi:10.2174/1568009617666170427104356


Author Mir, Nabiel
Jayachandran, Aparna
Dhungel, Bijay
Shrestha, Ritu
Steel, Jason C.
Title Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma
Journal name Current Cancer Drug Targets   Check publisher's open access policy
ISSN 1568-0096
Publication date 2017-01-01
Year available 2017
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/1568009617666170427104356
Open Access Status Not yet assessed
Volume 17
Issue 8
Start page 698
End page 706
Total pages 9
Place of publication SHARJAH
Publisher BENTHAM SCIENCE PUBL LTD
Language eng
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.
Keyword Drug-Resistance
Cancer-Cells
Liver-Cancer
Stem-Cells
Invasion
Growth
Emt
Immunotherapy
Opportunities
Doxorubicin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: WoS Import
 
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Created: Sun, 05 Nov 2017, 09:41:29 EST