Epigenetic Mechanisms Involved in the Pathogenesis of Hepatobiliary Malignancies

Abstract

Primary tumors of the liver and biliary tree are increasing in frequency and portend a miserable prognosis. Epigenetic regulation of gene expression has emerged as a fundamental aspect of cancer development and progression. The molecular mechanisms of carcinogenesis in hepatocellular carcinoma and cholangiocarcinoma involve a complex interplay of both genetic and epigenetic factors. Recent studies investigating the possible epigenetic mechanisms induced in the disease have shed new light on the molecular underpinnings of hepatobiliary cancers. In addition, epigenetic modifications of DNA in cancer and precancerous lesions offer hope and the promise of novel biomarkers for early cancer detection, prediction, prognosis and response to treatment. Furthermore, the reversal of epigenetic changes represents a potential target for novel therapeutic strategies and medication design.

KEYWORDS::

• 5-azacytidine
• cholangiocarcinoma
• epigenetics
• HCC
• hepatocellular carcinoma
• histone modification
• hypermethylation
• hypomethylation
• methylation
• p16
• RAS
• sorafenib
• zebularine

Acknowledgements

The author would like to thank Stephen J Meltzer for his inspiration, tutelage and support.

Financial & competing interests disclosure

James P Hamilton is supported by a Clinician Scientist Award from The Johns Hopkins University School of Medicine and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (1K08DK083774). He has also served on a Scientific Advisory board for Bayer (Onyx) and Gilead. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

James P Hamilton is supported by a Clinician Scientist Award from The Johns Hopkins University School of Medicine and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (1K08DK083774). He has also served on a Scientific Advisory board for Bayer (Onyx) and Gilead. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.