To overcome the resistance induced by an isoform switching mutation, the possibility to use the anti-IDH2 Enasidenib (yet approved for AML-resistant clones), the association between Enasidenib and Ivosidenib (anti-IDH1 plus anti-IDH2), and the use of dual inhibitors like Vorasidenib have been explored as promising strategies in AML and glioma, while in iCCA, the data are still insufficient [56,95]. The gene discussed is IDH2; the disease is glioma.