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Mitochondrial targets in IDH1-mutated cholangiocarcinoma.

ABSTRACT: Cholangiocarcinoma (CCA), a subset of biliary tract cancers, remains a therapeutically challenging malignancy with poor long-term survival despite recent advances in targeted therapies. Recent data suggest that IDH1-mutated CCA exhibits unique mitochondrial vulnerabilities. In this report, we discuss the emerging role of mitochondrial metabolism as a target in IDH1-mutated CCA, including preclinical evidence supporting the inhibition of the tricarboxylic acid (TCA) cycle, glutamine metabolism, and potential combination approaches. We aim to highlight the growing need to integrate mitochondrial-targeted strategies into future clinical investigations.

SUBMITTER: Carvalho C 

PROVIDER: S-EPMC12947996 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature

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Mitochondrial targets in IDH1-mutated cholangiocarcinoma.

Carvalho Camila C   Wuchu Fulei F   Peterson Nicole N   Nagrath Deepak D   Mohan Arathi A   Sahai Vaibhav V  

Hepatology communications 20260226 3

Cholangiocarcinoma (CCA), a subset of biliary tract cancers, remains a therapeutically challenging malignancy with poor long-term survival despite recent advances in targeted therapies. Recent data suggest that IDH1-mutated CCA exhibits unique mitochondrial vulnerabilities. In this report, we discuss the emerging role of mitochondrial metabolism as a target in IDH1-mutated CCA, including preclinical evidence supporting the inhibition of the tricarboxylic acid (TCA) cycle, glutamine metabolism, a  ...[more]