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Histone Deacetylases: the Biology and Clinical Implication pp 13–37Cite as

The Biology of HDAC in Cancer: The Nuclear and Epigenetic Components

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 206))

Abstract

Traditionally, cancer has been regarded to originate from genetic alterations such as mutations, deletions, rearrangements as well as gene amplifications, leading to abnormal expression of tumor suppressor genes and oncogenes. An increasing body of evidence indicates that in addition to changes in DNA sequence, epigenetic alterations contribute to cancer initiation and progression. In contrast to genetic mutations, epigenetic changes are reversible and therefore an attractive target for cancer therapy. Many epi-drugs such as histone deacetylase (HDAC) inhibitors showed anticancer activity in cell culture and animal models of carcinogenesis. Recently, the two HDAC inhibitors suberoylanilide hydroxamic acid (SAHA, Vorinostat) and Romidepsin (Depsipeptide, FK228) were FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL). Although HDAC inhibitors are potent anticancer agents, these compounds act against several HDAC family members potentially resulting in numerous side effects. This stems from the fact that HDACs play crucial roles in a variety of biological processes including cell cycle progression, proliferation, differentiation, and development. Consistently, mice deficient in single HDACs mostly exhibit severe phenotypes. Therefore, it is necessary to specify the cancer-relevant HDACs in a given tumor type in order to design selective inhibitors that target only cancer cells without affecting normal cells. In this chapter, we summarize the current state of knowledge of individual nuclear HDAC family members in development and tumorigenesis, their contribution to the hallmarks of cancer, and the involvement of HDAC family members in different types of human malignancies.

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Acknowledgments

The authors would like to apologize to all colleagues whose work could not be cited due to space limitations. We would like to thank Sabine Lagger, Mircea Winter, Mirjam Moser, and Nicole Foeger for critical comments on the manuscript.

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  1. Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Vienna, Austria

    Astrid Hagelkruys, Anna Sawicka, Magdalena Rennmayr & Christian Seiser

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  1. Astrid Hagelkruys
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  2. Anna Sawicka
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  3. Magdalena Rennmayr
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  4. Christian Seiser
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Correspondence to Christian Seiser .

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  1. , Department of Pharmacology, Duke University, Durham, 27710, North Carolina, USA

    Tso-Pang Yao

  2. , Department of Molecular Oncology, H.Lee Moffitt Cancer Center & Research I, Magnolia Drive 12902, Tampa, 33612, Florida, USA

    Edward Seto

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Hagelkruys, A., Sawicka, A., Rennmayr, M., Seiser, C. (2011). The Biology of HDAC in Cancer: The Nuclear and Epigenetic Components. In: Yao, TP., Seto, E. (eds) Histone Deacetylases: the Biology and Clinical Implication. Handbook of Experimental Pharmacology, vol 206. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21631-2_2

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