Reference Detail

Ref Type Journal Article
PMID (26396249)
Authors Lopez G, Song Y, Lam R, Ruder D, Creighton CJ, Bid HK, Bill KL, Bolshakov S, Zhang X, Lev D, Pollock RE
Title HDAC Inhibition for the Treatment of Epithelioid Sarcoma: Novel Cross Talk Between Epigenetic Components.
Journal Molecular cancer research : MCR
Vol 14
Issue 1
Date 2016 Jan
URL
Abstract Text Epithelioid sarcoma is a rare neoplasm uniquely comprised of cells exhibiting both mesenchymal and epithelial features. Having propensity for local and distant recurrence, it poses a diagnostic dilemma secondary to pathologic complexity. Patients have dismal prognosis due to lack of effective therapy. HDAC inhibitors (HDACi) exhibit marked antitumor effects in various malignancies. The studies here demonstrate that pan-HDAC inhibitors constitute novel therapeutics versus epithelioid sarcoma. Human ES cells (VAESBJ, HS-ES, Epi-544) were studied in preclinical models to evaluate HDACi effects. Immunoblot and RT-PCR were used to evaluate expression of acetylated tubulin, histones H3/H4, EZH2 upon HDACi. MTS and clonogenic assays were used to assess the impact of HDACi on cell growth. Cell culture assays were used to evaluate the impact of HDACi and EZH2-specific siRNA inhibition on cell-cycle progression and survival. Unbiased gene array analysis was used to identify the impact of HDACi on epithelioid sarcoma gene expression. Xenografts were used to evaluate epithelioid sarcoma tumor growth in response to HDACi. HDAC inhibition increased target protein acetylation and abrogated cell growth and colony formation in epithelioid sarcoma cells. HDACi induced G(2) cell-cycle arrest and marked apoptosis, and reduced tumor growth in xenograft models. HDACi induced widespread gene expression changes, and EZH2 was significantly downregulated. EZH2 knockdown resulted in abrogated cell growth in vitro.The current study suggests a clinical role for HDACi in human epithelioid sarcoma, which, when combined with EZH2 inhibitors, could serve as a novel therapeutic strategy for epithelioid sarcoma patients. Future investigations targeting specific HDAC isoforms along with EZH2 may potentially maximizing treatment efficacy.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown epithelioid sarcoma not applicable Vorinostat Preclinical Actionable In a preclinical study, Zolinza (vorinostat) inhibited growth and colony formation of epithelioid sarcoma cells in culture (PMID: 26396249). 26396249
Unknown unknown epithelioid sarcoma not applicable Abexinostat Preclinical - Cell line xenograft Actionable In a preclinical study, Abexinostat (PCI-24781) inhibited growth and colony formation of epithelioid sarcoma cell lines in culture, and inhibited tumor growth in epithelioid sarcoma cell line xenograft models (PMID: 26396249). 26396249
Unknown unknown epithelioid sarcoma not applicable Entinostat Preclinical Actionable In a preclinical study, Entinostat inhibited growth and colony formation of epithelioid sarcoma cells in culture (PMID: 26396249). 26396249