Methods of stratifying patients for treatment with retinoic acid receptor-alpha agonists
AssigneeSyros Pharmaceuticals, Inc.
InventorsMei Wei Chen, Cindy Collins, Matthew Lucas Eaton, Matthew G. Guenther, Nan Ke, Jeremy Lopez, Michael Robert McKeown, David A. Orlando
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Abstract
The invention provides methods that define cellular populations that are sensitive to RARA agonists and identify patient subgroups that will benefit from treatment with RARA agonists. The invention also provides packaged pharmaceutical compositions that comprise a RARA agonist and instructions for determining if such agonist is suitable for use in treatment.
Claims27
A method of treating myelodysplastic syndrome (MDS) in a subject, the method comprising administering a therapeutically effective amount of tamibarotene to the subject, wherein, prior to administration, a sample of diseased cells from the subject is determined to have
- (a) a super enhancer associated with a retinoic acid receptor alpha (RARA) gene, wherein the super enhancer has a strength or ordinal rank that is equal to or above a pre-determined threshold level;
- or
- (b) a level of primary RNA transcripts from the RARA gene and/or a portion of the super enhancer associated therewith, wherein the level of the RNA transcripts is equal to or above a pre-determined threshold, and wherein the RNA transcripts are transcribed from a RARA gene that encodes a functional RARA and specifically excludes gene fusions that comprise all or a portion of the RARA gene.
Dependencies are inferred from the claim text.