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Histone Deacetylase Inhibitors and Tumor Radiosensitization

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Increasing the Therapeutic Ratio of Radiotherapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Current strategies to increase the radiosensitivity of tumor cells have focused on the molecules and pathways that regulate response to radiation at the cellular level. One group of processes that is generating considerable interest is the modification of DNA histones, with a particular focus on the inhibition of histone acetylation. Histone acetylation is the process by which an acetyl group is covalently affixed to lysine residues within the N-terminus of histone proteins. Acetylation levels are determined by the opposing actions of two families of enzymes: histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs function to regulate both chromatin structure and gene expression, two factors that are important in determining the response of tumors to radiation. In an attempt to alter the histone acetylation status of cells, considerable efforts at the development of inhibitors of HDAC activity have occurred. The result is the development of a large and structurally diverse number of compounds that are able to inhibit HDAC activity, leading to the hyperacetylation of histones. In preclinical studies, these compounds have been found to enhance the in vitro and in vivo radiosensitivity of a spectrum of human tumor lines. Although the mechanism of HDAC inhibitor-induced radiosensitization has not been fully elucidated, HDAC inhibitors have shown promise in clinical trials when used in combination with chemotherapy and radiation therapy.

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  1. Radiation Oncology Branch, National Cancer Institute, 10 Center Drive, MSC 1002, Building 10, B3B69B, Bethesda, MD, 20892, USA

    Elizabeth I. Spehalski, Philip J. Tofilon & Kevin Camphausen

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  1. Elizabeth I. Spehalski
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  2. Philip J. Tofilon
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  1. Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA

    Philip J. Tofilon

  2. 1Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA

    Kevin Camphausen

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Spehalski, E.I., Tofilon, P.J., Camphausen, K. (2017). Histone Deacetylase Inhibitors and Tumor Radiosensitization. In: Tofilon, P., Camphausen, K. (eds) Increasing the Therapeutic Ratio of Radiotherapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-40854-5_3

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