Methods and compositions for cell-proliferation-related disorders

Abstract

Methods of treating and evaluating subjects having neoactive mutants are described herein.

1 . A method of treating a subject having an astrocytic tumor, an oligodendroglial tumor, an oligoastrocytic tumor or an anaplastic astrocytoma characterized by the presence of a mutant isocitrate dehydrogenase 1 (IDH1), the method comprising administering to the subject a therapeutically effective amount of a small molecule inhibitor of said mutant IDH1 that inhibits the conversion of alpha-ketoglutarate to 2-hydroxyglutarate (2-HG), wherein the IDH1 mutant has a mutation selected from R132H, R132C, R132S, R132G, R132L and R132V. 
     
     
         2 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the mutation is detected in a sample obtained from the subject. 
     
     
         10 . The method of  claim 9 , wherein the sample comprises tissue or bodily fluid. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 9 , wherein the mutation is detected by polymerase chain reaction (PCR). 
     
     
         13 - 18 . (canceled) 
     
     
         19 . A method of treating a subject having acute myelogenous leukemia (AML) characterized by the presence of a mutant isocitrate dehydrogenase 1 (IDH1), the method comprising administering to the subject a therapeutically effective amount of a small molecule inhibitor of said mutant IDH1, wherein the IDH1 mutant has a mutation selected from R132H, R132C, R132S, R132G, R132L, and R132V.