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Epigenetic Targeting and Histone Deacetylase Inhibition in RCC

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Renal Cell Carcinoma

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Abstract

Epigenetic regulation through histone modifications and DNA methylation of critical genes involved in cell cycle regulation, invasion, metastasis, and tumor-induced angiogenesis has been shown to play an important role in cancer development. Epigenetic changes are potentially reversible and therefore represent a target for therapeutic intervention with the potential of modulating oncogenes/tumor suppressor genes involved in the initiation and progression of cancer. Rational combination strategies that take advantage of transcriptional and posttranslational modifications induced by histone deacetylase inhibitors have generated promising preclinical results and are actively being tested in clinical trials. Preclinical and clinical evidence suggests that kidney tumors are ideal candidates for epigenetic therapies in view of specific mutations in histone modifier genes, overexpression of angiogenesis factors, and intrinsic sensitivity to immunotherapies. This chapter focuses on epigenetic changes in renal cell carcinoma (RCC) and, in particular, on histone modifications and therapeutic approaches currently underway targeting these epigenetic changes.

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Authors and Affiliations

  1. Genitourinary Program, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY, USA

    Swathi Ramakrishnan M.S.

  2. Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263-0001, USA

    Roberto Pili M.D.

Authors
  1. Swathi Ramakrishnan M.S.
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  2. Roberto Pili M.D.
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Correspondence to Roberto Pili M.D. .

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Editors and Affiliations

  1. David Geffen School of Medicine at UCLA, Department of Medicine, Cedars-Sinai Medical Center, n/a, Los Angeles, 90095, California, USA

    Robert A. Figlin

  2. Lineberger Comprehensive Cancer Center, University of North Carolina, Campus Box 7295, Room 21-237, 218, Chapel Hill, 27599-7295, North Carolina, USA

    W. Kimryn Rathmell

  3. Taussig Cancer Institute, Department of Solid Tumor Oncology, Cleveland Clinic, 9500 Euclid Ave, CLEVELAND, 44195-0001, Ohio, USA

    Brian I. Rini

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Ramakrishnan, S., Pili, R. (2012). Epigenetic Targeting and Histone Deacetylase Inhibition in RCC. In: Figlin, R., Rathmell, W., Rini, B. (eds) Renal Cell Carcinoma. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2400-0_9

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