IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced nicotinamide adenine dinucleotide phosphate (NADPH) from NADP+. Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the 'oncometabolite' R(-)-2-hydroxyglutarate (2HG). 2-HG competitively inhibits α-KG-dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials and have shown encouraging results in patients with IDH2 mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.
from Cancer via ola Kala on Inoreader http://ift.tt/1KGxBEa
via IFTTT
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου