Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (24231268)
Authors Henssen A, Thor T, Odersky A, Heukamp L, El-Hindy N, Beckers A, Speleman F, Althoff K, Schafers S, Schramm A, Sure U, Fleischhack G, Eggert A, Schulte JH
Title BET bromodomain protein inhibition is a therapeutic option for medulloblastoma.
Journal Oncotarget
Vol 4
Issue 11
Date 2013 Nov
URL
Abstract Text Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its pathogenetic role in medulloblastoma. Recent studies using the selective small molecule BET inhibitor, JQ1, have identified BET bromodomain proteins, especially BRD4, as epigenetic regulatory factors for MYC and its targets. Targeting MYC expression by BET inhibition resulted in antitumoral effects in various cancers. Our aim here was to evaluate the efficacy of JQ1 against preclinical models for high-risk MYC-driven medulloblastoma. Treatment of medulloblastoma cell lines with JQ1 significantly reduced cell proliferation and preferentially induced apoptosis in cells expressing high levels of MYC. JQ1 treatment of medulloblastoma cell lines downregulated MYC expression and resulted in a transcriptional deregulation of MYC targets, and also significantly altered expression of genes involved in cell cycle progression and p53 signalling. JQ1 treatment prolonged the survival of mice harboring medulloblastoma xenografts and reduced the tumor burden in these mice. Our preclinical data provide evidence to pursue testing BET inhibitors, such as JQ1, as molecular targeted therapeutic options for patients with high-risk medulloblastomas overexpressing MYC or harboring MYC amplifications.

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
JQ1 JQ1 8 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
JQ1 JQ-1 BET Inhibitor (Pan) 32 JQ1 is a BET bromodomain inhibitor with greatest specificity towards BRD4, resulting in decreased Myc expression, increased cell death, reduced macrophage immunosuppression, and inhibition of tumor growth (PMID: 24231268, PMID: 31018997, PMID: 30906568, PMID: 32800944).
Gene 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
TP53 mutant medulloblastoma decreased response JQ1 Preclinical Actionable In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). 24231268
TP53 wild-type medulloblastoma sensitive JQ1 Preclinical Actionable In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). 24231268