ArticleNPJ precision oncology2022
Secondary IDH1 resistance mutations and oncogenic IDH2 mutations cause acquired resistance to ivosidenib in cholangiocarcinoma.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Evolving precision: Updates in targeted therapy for cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2026Review
- Circulating tumor DNA-based detection of molecular residual disease in isocitrate dehydrogenase-mutant cholangiocarcinoma for biomarker-guided therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Clinical and molecular response to vorasidenib in post-transplant patient with IDH2-mutant intrahepatic cholangiocarcinoma.The oncologist · 2026Article
- Clinical relevance of mosaic variants detected by exome sequencing.The Journal of allergy and clinical immunology · 2026Article
- Review
- MAPK Pathway Mutations Emerge in Mutant IDH1 Inhibitor-Resistant Cholangiocarcinoma and Attenuate the IFN Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Mitochondrial targets in IDH1-mutated cholangiocarcinoma.Hepatology communications · 2026Review
- Mutant Isocitrate Dehydrogenase 1 Sensitizes Intrahepatic Cholangiocarcinoma Cells to MDM2 Inhibitors.Cancer research communications · 2026Article
- Evaluation of the Idylla IDH1-2 Mutation Assay for the Detection ofInternational journal of molecular sciences · 2026Article
- The role of ADAM8 in intrahepatic cholangiocarcinoma.Discover oncology · 2025Review
- Chronic Liver Disease Associated Cholangiocarcinoma: Genomic Insights and Precision Therapeutic Strategies.Cancers · 2025Review
- The bile duct and liver cancer: ON-treatment surveillance of tumor evolution and response to systemic treatment (BILLIONSTARS) study.BMC cancer · 2025Observational
- New systemic treatment paradigms in advanced biliary tract cancer and variations in patient access across Europe.The Lancet regional health. Europe · 2025Review
- Cholangiocarcinoma Targeted Therapies: Mechanisms of Action and Resistance.The American journal of pathology · 2025Review
- The IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury by promoting ferroptosis through disrupting NDUFA1 and FSP1 interaction.Cell death and differentiation · 2025Article
- IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies.Current oncology (Toronto, Ont.) · 2025Review
- Digestive cancers: mechanisms, therapeutics and management.Signal transduction and targeted therapy · 2025Review
- Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.Frontiers in immunology · 2025Review
- Circulating tumor DNA in cholangiocarcinoma: current clinical applications and future perspectives.Frontiers in cell and developmental biology · 2025Review
- ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells.NPJ precision oncology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
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 ivosidenib is impaired and it retains the ability to produce (R)-2HG and promote cellular transformation in the presence of ivosidenib. The irreversible mutant IDH1 inhibitor LY3410738 binds and blocks (R)-2HG production and cellular transformation by IDH1 R132H/D279N. These resistance mechanisms suggest that IDH1-mutated cholangiocarcinomas remain dependent on (R)-2HG even after prolonged ivosidenib treatment. Sequential mutant IDH inhibitor therapy should be explored as a strategy to overcome acquired resistance to mutant IDH inhibitors.
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Registered trials
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