Third, the substitution of R132 with any one of the six amino acids observed in gliomas (His, Ser, Gly, Cys, Val, and Leu) may have a dramatically reduced affinity for isocitrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers, making the cell more susceptible to the oxidative stress induced by chemotherapy and radiotherapy [42]. Here, IDH1 is linked to glioma.