Non-canonical SWI/SNF complex and uses thereof
AssigneeDana-Farber Cancer Institute, Inc.
InventorsCigall Kadoch, Brittany C. Michel, Andrew D'Avino
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Abstract
The present invention provides compositions and methods for treating cancers with canonical BAF (cBAF) complex perturbations (e.g. synovial sarcoma or malignant rhabdoid tumor) using an agent that inhibits the formation, activity, and/or stability of the ncBAF complex.
Claims13
A method of treating a subject afflicted with a cancer that has a reduced copy number, amount, and/or activity of a core cBAF component, wherein the core cBAF component is selected from the group consisting of ARID1A, ARID1B, and SMARCE1,
- the method comprising administering to the subject a therapeutically effective amount of a nucleic acid agent that comprises a nucleotide sequence that is homologous to the nucleotide sequence of GLTSCR1 or a portion thereof,
- wherein the nucleic acid agent downregulates the copy number or amount of GLTSCR1 and thereby inhibits the formation, activity, and/or stability of noncanonical BAF (ncBAF) complex, and/or the binding of ncBAF complex to chromatin or other proteins;
- wherein the nucleic acid agent (a) is selected from the group consisting of an siRNA, an shRNA, and a gRNA, and (b) comprises a sequence set forth in any one of SEQ ID NOs:
- 47-50.
A method of reducing viability or proliferation of cancer cells having a reduced copy number, amount, and/or activity of a core cBAF component, wherein the core cBAF component is selected from the group consisting of ARIDIA, ARID1B, and SMARCE1,
- the method comprising contacting the cancer cells with a nucleic acid agent that comprises a nucleotide sequence that is homologous to the nucleotide sequence of GLTSCR1 or a portion thereof,
- wherein the nucleic acid agent downregulates the copy number or amount of GLTSCR1 and thereby inhibits the formation, activity, and/or stability of ncBAF complex, and/or the binding of ncBAF complex to chromatin or other proteins;
- wherein the nucleic acid agent (a) is selected from the group consisting of an siRNA, an shRNA, and a gRNA, and (b) comprises a sequence set forth in any one of SEQ ID NOs:
- 47-50.
Dependencies are inferred from the claim text.