	US 11,998,540 B2
	Compositions and methods for treating drug-tolerant glioblastoma
Brian B. Liau, Boston, MA (US); Anoop P. Patel, Boston, MA (US); Cem Sievers, Boston, MA (US); and Bradley E. Bernstein, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Appl. No. 16/060,852
Filed by THE GENERAL HOSPITAL CORPORATION, Boston, MA (US)
PCT Filed Mar. 24, 2016, PCT No. PCT/US2016/024083 § 371(c)(1), (2) Date Jun. 8, 2018, PCT Pub. No. WO2017/099829, PCT Pub. Date Jun. 15, 2017.
Claims priority of provisional application 62/266,544, filed on Dec. 11, 2015.
Prior Publication US 2019/0000831 A1, Jan. 3, 2019
Int. Cl. A61K 31/4709 (2006.01); A61K 31/44 (2006.01); A61K 31/506 (2006.01); A61K 31/55 (2006.01); A61K 31/5513 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01)

CPC A61K 31/4709 (2013.01) [A61K 31/44 (2013.01); A61K 31/506 (2013.01); A61K 31/55 (2013.01); A61K 31/5513 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); A61K 2300/00 (2013.01)]

1 Claim

1. A method of increasing cell death in a glioblastoma stem cell population comprising measuring expression in the glioblastoma stem cell population of one or more biomarkers selected from the group consisting of SALL2, DLX2, ZFHX4, HEY1, HES5, and FABP7 in the glioblastoma stem cell population;

contacting the glioblastoma stem cell population with dasatinib, crenolanib, or a combination thereof,

wherein dasatinib has the following structure:

and crenolanib has the following structure:

measuring expression of said one or more biomarkers in in the glioblastoma stem cell population after said contacting with dasatinib, crenolanib, or a combination thereof; and

contacting the glioblastoma stem cell persister population with GSKJ4 if there is increased expression of said one or more biomarkers after said contacting with dasatinib, crenolanib, or a combination thereof as compared to the first measuring step, wherein,

GSKJ4 has the following structure: