Molecular pathology for cholangiocarcinoma: a review of actionable genetic targets and their relevance to adjuvant & neoadjuvant therapy, staging, follow-up, and determination of minimal residual disease.

Autor:	Warren EAK; Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA., Maithel SK; Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Jazyk:	angličtina
Zdroj:	Hepatobiliary surgery and nutrition [Hepatobiliary Surg Nutr] 2024 Feb 01; Vol. 13 (1), pp. 29-38. Date of Electronic Publication: 2023 Mar 24.
DOI:	10.21037/hbsn-22-563
Abstrakt:	Cholangiocarcinoma (CCA) represents a group of epithelial cell tumors classified based on their anatomic location along the biliary tree. This rare malignancy is often diagnosed at an advanced stage and deemed unresectable. Even for those patients who are surgical candidates, recurrence rates are high and survival rates low. The mainstay of therapy for advanced CCA remains cisplatin plus gemcitabine, with a median overall survival (mOS) under 12 months, although the TOPAZ-1 trial showed a survival benefit with the addition of programmed cell death ligand 1 (PD-L1) blockade. In recent years, molecular profiling has revealed a wealth of potentially targetable genetic alterations, including fibroblast growth factor receptor ( FGFR ) fusions, isocitrate dehydrogenase 1 ( IDH1 ) mutations, human epidermal growth factor receptor 2 ( HER2 ) amplification and overexpression, and microsatellite instability (MSI). These discoveries have prompted numerous clinical trials employing drugs against these specific genetic changes. The foundation laid by early clinical studies and the landscape of ongoing trials are both summarized here. While the role of adjuvant therapy has yet to be defined in this disease, we emphasize the importance of employing targeted therapies in trials in the adjuvant and neoadjuvant spaces and discuss ways to overcome challenges due to low incidence of targetable mutations. Personalized medicine for this disease promises significant clinical benefit to patients, but further investigation is needed. Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-563/coif). The series “Molecular, Protein, and Cellular Markers for HPB Cancers” was commissioned by the editorial office without any funding or sponsorship. S.K.M. serves as the unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The authors have no other conflicts of interest to declare. (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)
Databáze:	MEDLINE
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