METHODS AND COMPOSITIONS FOR CELL-PROLIFERATION-RELATED DISORDERS
Methods of treating and evaluating subjects having neoactive mutants are described herein.
1 . A method of treating a subject having a cancer characterized by the presence of a mutant isocitrate dehydrogenase 1 enzyme (IDH1) or a mutant isocitrate dehydrogenase 2 enzyme (IDH2), wherein the mutant IDH1 or mutant IDH2 has the ability to convert alpha-ketoglutarate to 2-hydroxyglutarate (2HG), the method comprising administering to the subject a therapeutically effective amount of an inhibitor of said mutant IDH1 or mutant IDH2.
2 . The method of claim 1 , wherein the inhibitor binds to IDH1R132X or IDH2R172X and inhibits the ability to convert alpha-ketoglutarate to 2-HG.
3 . The method of claim 1 , wherein the cancer is characterized by an IDH1 mutation.
4 . The method of claim 3 , wherein the IDH1 mutation is an IDH1R132X mutation.
5 . The method of claim 3 , wherein the IDH1 mutation is selected from R132H, R132C, R132S, R132G, R132L, and R132V.
6 . The method of claim 1 , wherein the cancer is characterized by an IDH2 mutation.
7 . The method of claim 6 , wherein the IDH2 mutation is an IDH1R172X mutation.
8 . The method of claim 6 , wherein the IDH2 mutation is selected from R172K, R172M, R172S, R172G, and R172W.
9 . The method of claim 1 , wherein the mutant IDH1 or mutant IDH2 is detected in a sample obtained from the subject.
10 . The method of claim 9 , wherein the sample comprises tissue or bodily fluid.
11 . The method of claim 1 , wherein the mutant IDH1 or mutant IDH2 is detected by sequencing a nucleic acid from an affected cell that encodes the relevant amino acid(s) from the mutant IDH1 or mutant IDH2.
12 . The method of claim 11 , wherein the sequencing is performed by polymerase chain reaction (PCR).
13 . The method of claim 1 , wherein the inhibitor is a small molecule compound.
14 . The method of claim 1 , wherein the cancer is selected from an astrocytic tumor, an oligodendroglial tumor, an oligoastrocytic tumor, an anaplastic astrocytoma, fibrosarcoma, paraganglioma, prostate cancer, acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML).
15 . The method of claim 1 , wherein the cancer is a glioblastoma.
16 . The method of claim 1 , wherein the cancer is a glioma.
17 . The method of claim 14 , wherein the cancer is AML.
18 . The method of claim 14 , wherein the ALL is B-cell ALL or T-cell ALL.