Research ArticleCancer

An Integrated Genomic and Epigenomic Approach Predicts Therapeutic Response to Zebularine in Human Liver Cancer

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Science Translational Medicine  20 Oct 2010:
Vol. 2, Issue 54, pp. 54ra77
DOI: 10.1126/scitranslmed.3001338

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A Crystal Ball for Cancer Therapy

If you ask most first-year medical students, they are not likely to list fortune-telling as a required skill for a successful clinician. Yet, predicting how different patients will respond to therapy could save time, money, and lives. Andersen et al. peer into their crystal ball and provide an approach for determining whether patients with liver cancer will respond to treatment or not.

Liver cancer causes more than half a million deaths annually. Although early cases may respond to treatment, it is often diagnosed at later stages when symptoms become more severe. Only a subset of patients with advanced-stage liver cancer is eligible for the most successful current therapy, sorafenib, leaving a large number of patients with few options. Epigenetic changes, or changes in gene expression not due to differences in DNA sequence, contribute to the initiation and progression of liver cancer. These changes are reversible, and epigenetic modifier drugs such as zebularine can reactivate tumor suppressor genes and decrease tumor cell growth.

Andersen et al. characterized the epigenetic changes induced by zebularine in liver cancer cell lines. They found a distinct signature that identified two groups of cells—those sensitive and those resistant to zebularine. In an animal xenograft model, zebularine treatment of liver tumors with the “sensitive” profile resulted in increased survival and decreased metastasis to the lungs. Moreover, the zebularine-sensitive signature predicted prognosis of patients with liver cancer with an accuracy ranging from 84 to 96%. Therefore, this study not only provides a proof of principle that epigenetic modification may be a viable therapy for liver cancer but also gives us a glimpse into the future, allowing clinicians to predict clinical outcome for liver cancer patients, as well as the success or failure of this emerging treatment regimen.

Footnotes

  • Citation: J. B. Andersen, V. M. Factor, J. U. Marquardt, C. Raggi, Y.-H. Lee, D. Seo, E. A. Conner, S. S. Thorgeirsson, An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer. Sci. Transl. Med. 2, 54ra77 (2010).

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