US 12,171,783 B2
Methods and compositions for targeting developmental and oncogenic programs in H3K27M gliomas
Mario Suva, Boston, MA (US); Bradley Bernstein, Boston, MA (US); Aviv Regev, Cambridge, MA (US); Mariella Filbin, Boston, MA (US); Itay Tirosh, Cambridge, MA (US); and Volker Hovestadt, Boston, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); The General Hospital Corporation, Boston, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Appl. No. 16/763,705
Filed by The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); The General Hospital Corporation, Boston, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
PCT Filed Nov. 13, 2018, PCT No. PCT/US2018/060799
§ 371(c)(1), (2) Date May 13, 2020,
PCT Pub. No. WO2019/094955, PCT Pub. Date May 16, 2019.
Claims priority of provisional application 62/586,093, filed on Nov. 14, 2017.
Claims priority of provisional application 62/585,468, filed on Nov. 13, 2017.
Prior Publication US 2020/0384022 A1, Dec. 10, 2020
Int. Cl. A61K 35/17 (2015.01); A61K 31/519 (2006.01); A61K 38/50 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01)
CPC A61K 35/17 (2013.01) [A61K 31/519 (2013.01); A61K 38/50 (2013.01); A61P 35/00 (2018.01); C07K 16/2863 (2013.01); C07K 16/3053 (2013.01); C07K 2317/31 (2013.01)] 11 Claims
 
1. A method of treating histone H3 lysine 27-to-methionine mutant glioma (H3K27M-glioma) in a subject, comprising: detecting an altered gene expression or activity of HENMT1 relative to a reference level in a gene signature of a plurality of H3K27M-glioma cells of the subject and administering to the subject either: 1) a small molecule inhibitor of BMI1 when the altered level of gene expression or activity of HENMT1 is increased or 2) a small molecule inhibitor that inhibits one or more PRC2 target genes when the altered level of gene expression or activity of HENMT1 is decreased.