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Current Approaches to Epigenetic Therapy for the Treatment of Mantle Cell Lymphoma

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Impact of Genetic Targets on Cancer Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((volume 779))

Abstract

Epigenetics is the study of heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence. Such changes can include DNA methylation or histone modifications which both serve to silence gene expression. This review describes a new development in pharmacology, epigenetic therapy, which attempts to correct these epigenetic changes for the treatment of mantle cell lymphoma (MCL) and other B cell malignancies for which no consensus on standard therapy exists. One class of drugs utilized are the histone deacetylase inhibitors, (HDACi) which result in the accumulation of acetylated histones. Hyperacetylation of histones and nonhistone proteins are postulated to mediate the anticancer effects of these drugs. Another class of epigenetic agents are hypomethylating agents, that can cause both DNA and histone hypomethylation. Epigenetic drugs may be useful in the treatment of cancer where hypermethylation of tumor suppressor genes is known to lead to silencing of these genes. The purine analog cladribine has been shown to have hypomethylating properties and has activity as a single agent or in combination with other therapies for mantle cell lymphoma. Epigenetic therapy with the DNA hypomethylating agent 5-aza-2-deoxycytidine can also cause restoration of cell surface expression of the CD20 protein and increase rituximab sensitivity in vitro. Combinations of epigenetic agents may act synergistically to further potentiate the efficacy of monoclonal antibodies like rituximab and ofatumumab and improve the treatment outcome in MCL.

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Authors and Affiliations

  1. Penn State Milton S. Hershey Medical Center, Hershey, PA, 17033, USA

    Vikas Ghai M.D., Kamal Sharma M.D., Kamal K. S. Abbi M.D., Sara Shimko BS & Elliot M. Epner M.D. Ph.D. (Professor of Medicine)

  2. Division of Hematology/Oncology, Penn State Hershey Cancer Institute and Penn State Hershey Medical Center, Hershey, PA, 17033, USA

    Elliot M. Epner M.D. Ph.D. (Professor of Medicine)

Authors
  1. Vikas Ghai M.D.
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  2. Kamal Sharma M.D.
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  3. Kamal K. S. Abbi M.D.
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  4. Sara Shimko BS
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  5. Elliot M. Epner M.D. Ph.D.
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Correspondence to Elliot M. Epner M.D. Ph.D. .

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Editors and Affiliations

  1. University Drive 500, Hershey, 17033, Pennsylvania, USA

    Wafik S El-Deiry

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Ghai, V., Sharma, K., Abbi, K.K.S., Shimko, S., Epner, E.M. (2013). Current Approaches to Epigenetic Therapy for the Treatment of Mantle Cell Lymphoma. In: El-Deiry, W. (eds) Impact of Genetic Targets on Cancer Therapy. Advances in Experimental Medicine and Biology, vol 779. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6176-0_11

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