US 11,896,678 B2
Compositions and methods for treatment of peroxisome proliferator-activated receptor gamma (PPARG) activated cancer
Jonathan Goldstein, Cambridge, MA (US); Matthew Meyerson, Boston, MA (US); and Craig Strathdee, Cambridge, MA (US)
Assigned to Dana-Farber Cancer Institute, Inc., Boston, MA (US); and The Broad Institute, Inc., Cambridge, MA (US)
Appl. No. 16/498,860
Filed by THE BROAD INSTITUTE, INC., Cambridge, MA (US); and DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
PCT Filed Mar. 28, 2018, PCT No. PCT/US2018/024970
§ 371(c)(1), (2) Date Sep. 27, 2019,
PCT Pub. No. WO2018/183580, PCT Pub. Date Oct. 4, 2018.
Claims priority of provisional application 62/478,380, filed on Mar. 29, 2017.
Prior Publication US 2020/0179534 A1, Jun. 11, 2020
Int. Cl. A61K 45/06 (2006.01); G01N 33/574 (2006.01); A61K 48/00 (2006.01); A61K 38/46 (2006.01); C12N 5/09 (2010.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01)
CPC A61K 48/0025 (2013.01) [A61K 38/465 (2013.01); A61K 45/06 (2013.01); C12N 5/0693 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); G01N 33/57492 (2013.01); C12N 2310/20 (2017.05); C12N 2800/80 (2013.01); G01N 2333/70567 (2013.01)] 15 Claims
 
1. A method of treating a subject diagnosed with a peroxisome proliferator-activated receptor gamma (PPARG) activated cancer, comprising:
performing an assay to determine the identity of an amino acid at position 447 of PPARG and position 427 of retinoid X receptor alpha (RXRA), wherein a PPARG reference amino acid at position 447 is threonine (T) and a RXRA reference amino acid at position 427 is serine (S);
detecting the presence of a PPARG amino acid variation relative to the PPARG reference amino acid, wherein the PPARG amino acid variation is methionine (M) and a RXRA amino acid variation relative to the RXRA reference amino acid, wherein the RXRA amino acid variation is phenylalanine (F) or tyrosine (Y); and
administering a therapeutically effective amount of a PPARG signaling modulator to the subject having a PPARG T447M variation and/or a RXRA S427F/Y variation.