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The Histone Deacetylase Inhibitor Entinostat/Syndax 275 in Osteosarcoma

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Current Advances in Osteosarcoma

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1257))

Abstract

The prognosis for metastatic osteosarcoma (OS) is poor and has not changed in several decades. Therapeutic paradigms that target and exploit novel molecular pathways are desperately needed. Recent preclinical data suggests that modulation of the Fas/FasL pathway may offer benefit in the treatment of refractory osteosarcoma. Fas and FasL are complimentary receptor-ligand proteins. Fas is expressed in multiple tissues, whereas FasL is restricted to privilege organs, such as the lung. Fas expression has been shown to inversely correlate with the metastatic potential of OS cells; tumor cells which express high levels of Fas have decreased metastatic potential and the ones that reach the lung undergo cell death upon interaction with constitutive FasL in the lung. Agents such as gemcitabine and the HDAC inhibitor, entinostat/Syndax 275, have been shown to upregulate Fas expression on OS cells, potentially leading to decreased OS pulmonary metastasis and improved outcome. Clinical trials are in development to evaluate this combination as a potential treatment option for patients with refractory OS.

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Authors and Affiliations

  1. Department of Pediatrics Research, MD Anderson Cancer Center, Houston, TX, USA

    Simin Kiany & Nancy Gordon

  2. Department of Pediatrics – Patient Care, MD Anderson Cancer Center, Houston, TX, USA

    Douglas Harrison

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  1. Simin Kiany
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  2. Douglas Harrison
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  3. Nancy Gordon
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Correspondence to Nancy Gordon .

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Editors and Affiliations

  1. Department of Pediatric Research, Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Eugenie S. Kleinerman

  2. Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Richard Gorlick

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Kiany, S., Harrison, D., Gordon, N. (2020). The Histone Deacetylase Inhibitor Entinostat/Syndax 275 in Osteosarcoma. In: Kleinerman, E.S., Gorlick, R. (eds) Current Advances in Osteosarcoma . Advances in Experimental Medicine and Biology, vol 1257. Springer, Cham. https://doi.org/10.1007/978-3-030-43032-0_7

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