Korean J Pancreas Biliary Tract.  2023 Jul;28(3):59-66. 10.15279/kpba.2023.28.3.59.

Recent Update of Targeted Therapy in Cholangiocarcinoma

• Lee J
• Kim DU

• KMID: 2544814
• DOI: http://doi.org/10.15279/kpba.2023.28.3.59

Abstract

Cholangiocarcinoma (CCA) is one of the cancers with the worst prognosis. Its incidence and mortality have increased in recent years, but treatment options are limited. Although various clinical trials have been conducted, there is no effective therapeutic agent yet. As molecular genetic profiling is progressing in CCA, the interest in targeted therapies is growing. To realize targeted therapy in practice, various clinical requirements must be met. A molecular biological test should be performed on a patient’s tissue or blood, a target should be determined using an appropriate analysis method, and there should be a targeted agent. Regarding CCA, genetic variation occupies an intermediate level. Accordingly, many new agents have been recently developed for molecular biological targets. The most common genetic aberrations show almost similar patterns in intrahepatic and extrahepatic CCA. However, HER2 gene amplification is more often observed in extrahepatic CCA, and FGFR2 fusion, IDH1 mutation, and RAS-RAF-MEK-ERK signaling system mutations are more frequently found in intrahepatic CCA. Phase 2 or 3 clinical trials are being conducted with zanidatamab for HER2 amplification, pemigatinib/infigratinib for FGFR fusion, ivosidenib for IDH1 mutation, and dabrafenib for BRAFV600E mutation. In addition, clinical trials for agents targeting the NTRK, BRCA, and ARID1A gene mutations are ongoing. These targeted therapies are expected to have a bright future as a new treatment for CCA.

Keyword

Cholangiocarcinoma; Molecular targeted therapy; Immunological antineoplastic agents; Precision medicine; Mutation; 담관암; 분자표적요법; 면역항암화학제; 정밀의학; 돌연변이