IDH1 and IDH2 mutations as friends and foes in human cancer

The enzyme isocytrate dehydrogenase IDH is very important in carbohydrate metabolism, and when mutated in cancer cells, the metabolic pathway is drastically altered. Somatic mutations in IDH1/2 occur in ~20% of patients with myeloid neoplasms, including glioma, melanoma, prostate cancer and acute myeloid leukemia. Cancer patients with IDH1/2 mutations have a relatively prolonged survival compared with IDH1/2 wild-type counterparts. The underlying molecular mechanism in various subtypes of cancer have been demonstrated to also involve altered redox homeostasis and reduced DNA damage repair. Furthermore, the ongoing clinical trials in which we repurpose already-approved and off-patent drugs for the treatment of IDH1/2-mutated cancers will be discussed.