Inhibition of histone deacetylase 2 reduces MDM2 expression and reduces tumor growth in dedifferentiated liposarcoma.

Inhibition of histone deacetylase 2 reduces MDM2 expression and reduces tumor growth in dedifferentiated liposarcoma. Oncotarget. 2019 Oct 01;10(55):5671-5679 Authors: Seligson ND, Stets CW, Demoret BW, Awasthi A, Grosenbacher N, Shakya R, Hays JL, Chen JL Abstract Dedifferentiated liposarcoma (DDLPS) is a highly morbid mesenchymal tumor characterized and driven by genomic amplification of the MDM2 gene. Direct inhibition of MDM2 has shown promise pre-clinically, but has yet to be validated in clinical trials. Early in vitro studies have demonstrated that pan-histone deacetylase (HDAC) inhibition may have anti-MDM2 effects. Here we present in silico, in vitro, and mouse xenograft studies that suggest that specifically targeting HDAC2 reduces MDM2 expression and has anti-tumor affects in DDLPS. Two independent datasets, The Cancer Genome Atlas (TCGA; n = 58) and the Memorial Sloan-Kettering Cancer Center Dataset (MSKCC; n = 63), were used to identify the co-expression between class I HDACs and MDM2, and their clinical impact. HDAC2 was highly co-expressed with MDM2 (TCGA: Spearman's coefficient = 0.29, p = 0.03; MSKCC: Spearman's coefficient = 0.57, p
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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