Fang Wang

TL;DR: The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy, and isocitrate dehydrogenase 1 (IDH1), which is mutated in multiple human cancers, is examined.

TL;DR: Evidence is provided that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer, and a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDh2/ R140Q is developed.

TL;DR: It is shown that the targeted inhibitor AG-221 suppresses the mutant IDH2 enzyme in multiple preclinical models and induces differentiation of malignant blasts, supporting its clinical development.

TL;DR: AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo is reported.

TL;DR: Results indicate that IDH2 mutant inhibition may function as a cancer therapy via histone and DNA demethylation at genes involved in differentiation and tumorigenesis, indicating a selective modulation of relevant cancer genes by IDH mutations.