IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies
Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations in cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with the ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Current Oncology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1718-7729/32/1/44 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588724757594112 |
|---|---|
| author | Alexander Bray Vaibhav Sahai |
| author_facet | Alexander Bray Vaibhav Sahai |
| author_sort | Alexander Bray |
| collection | DOAJ |
| description | Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations in cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with the ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As a result, pharmacologic inhibition of mIDH has become an attractive therapeutic strategy in CCAs harboring this mutation. One such inhibitor, ivosidenib, has already undergone clinical validation and received FDA approval in this disease, but there is still much work to be done to improve outcomes in mIDH CCA patients. In this publication we will review the pathogenesis and treatment of mIDH CCA with special emphasis on novel agents and combinations currently under investigation. |
| format | Article |
| id | doaj-art-c6f4adad50324687b797fb39f3992929 |
| institution | Kabale University |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj-art-c6f4adad50324687b797fb39f39929292025-01-24T13:28:28ZengMDPI AGCurrent Oncology1198-00521718-77292025-01-013214410.3390/curroncol32010044IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future TherapiesAlexander Bray0Vaibhav Sahai1Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADivision of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USAMutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations in cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with the ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As a result, pharmacologic inhibition of mIDH has become an attractive therapeutic strategy in CCAs harboring this mutation. One such inhibitor, ivosidenib, has already undergone clinical validation and received FDA approval in this disease, but there is still much work to be done to improve outcomes in mIDH CCA patients. In this publication we will review the pathogenesis and treatment of mIDH CCA with special emphasis on novel agents and combinations currently under investigation.https://www.mdpi.com/1718-7729/32/1/44cholangiocarcinomamutant isocitrate dehydrogenasetargeted therapyivosidenib2-hydroxyglutarateR2HG |
| spellingShingle | Alexander Bray Vaibhav Sahai IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies Current Oncology cholangiocarcinoma mutant isocitrate dehydrogenase targeted therapy ivosidenib 2-hydroxyglutarate R2HG |
| title | IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies |
| title_full | IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies |
| title_fullStr | IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies |
| title_full_unstemmed | IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies |
| title_short | IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies |
| title_sort | idh mutant cholangiocarcinoma pathogenesis management and future therapies |
| topic | cholangiocarcinoma mutant isocitrate dehydrogenase targeted therapy ivosidenib 2-hydroxyglutarate R2HG |
| url | https://www.mdpi.com/1718-7729/32/1/44 |
| work_keys_str_mv | AT alexanderbray idhmutantcholangiocarcinomapathogenesismanagementandfuturetherapies AT vaibhavsahai idhmutantcholangiocarcinomapathogenesismanagementandfuturetherapies |