Shengfang Jin

TL;DR: It is shown that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of α-ketoglutarate to R(-)-2-hydroxyglutarate (2HG), and that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.

TL;DR: IDH1/2 mutations confer an enzymatic gain of function that dramatically increases 2-HG in AML, providing an explanation for the heterozygous acquisition of these mutations during tumorigenesis.

TL;DR: It is shown that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small molecule PKM2 activators inhibit growth of xenograft tumors and support the notion that small molecule activation ofPKM2 can interfere with anabolic metabolism.

TL;DR: The prevalence of IDH mutations in cancer is surveyed and current mechanistic understanding ofIDH mutations with implications for diagnostic and therapeutic development for the treatment of gliomas and AML is explored.

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.