Products/Services Used | Details | Operation |
---|---|---|
Custom Vector Construction> | … The lentiviral expression vector used to express the IDH1 variants (pMT040-IRES-PURO) was custom-made (Genscript). It contains a CMV promoter driving the expression of a single … | Get A Quote |
The mutant IDH1 inhibitor ivosidenib improves outcomes for patients with IDH1-mutated cholangiocarcinoma, but resistance inevitably develops. Mechanisms of resistance and strategies to overcome resistance are poorly understood. Here we describe two patients with IDH1 R132C-mutated metastatic cholangiocarcinoma who developed acquired resistance to ivosidenib. After disease progression, one patient developed an oncogenic IDH2 mutation, and the second patient acquired a secondary IDH1 D279N mutation. To characterize the putative IDH1 resistance mutation, cells expressing the double-mutant were generated. In vitro, IDH1 R132H/D279N produces (R)-2HG less efficiently than IDH1 R132H. However, its binding to ivosideni... More