MODELLING BET INHIBITOR RESISTANCE IN ACUTE MYELOID LEUKAEMIA
Grant number: 1085015 | Funding period: 2015 - 2018
Mutations in epigenetic regulators in AML not only imply a causative role for these proteins in AML but also provide potential targets for therapeutic intervention. One of the most promising epigenetic therapies to have emerged in the last decade are small molecule inhibitors targeted to the Bromodomain and Extra Terminal (BET) family of proteins. This proposal will elucidate the cellular and molecular mechanisms that drive resistance to this new class of drugs
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Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in..
An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer
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Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia
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Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it..
CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid YN Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillanc..
Click chemistry enables preclinical evaluation of targeted epigenetic therapies
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The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BE..
Functional interdependence of BRD4 and DOT1L in MLL leukemia
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Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are current..
BET inhibitor resistance emerges from leukaemia stem cells
Chun Yew Fong, Omer Gilan, Enid YN Lam, Alan F Rubin, Sarah Ftouni, Dean Tyler, Kym Stanley, Devbarna Sinha, Paul Yeh, Jessica Morison, George Giotopoulos, Dave Lugo, Philip Jeffrey, Stanley Chun-Wei Lee, Christopher Carpenter, Richard Gregory, Robert G Ramsay, Steven W Lane, Omar Abdel-Wahab, Tony Kouzarides
Bromodomain and extra terminal protein (BET) inhibitors are first-in-class targeted therapies that deliver a new therapeutic oppor..