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Review
. 2022 Apr;11(2):253-266.
doi: 10.21037/hbsn-20-475.

Novel biomarkers and the future of targeted therapies in cholangiocarcinoma: a narrative review

Nishant Munugala  1 , Shishir K Maithel  2 , Rachna T Shroff  3
Affiliations
Review

Novel biomarkers and the future of targeted therapies in cholangiocarcinoma: a narrative review

Nishant Munugala et al. Hepatobiliary Surg Nutr. 2022 Apr.

Abstract

Background and objectives: Cholangiocarcinoma is a highly aggressive and heterogenous group of biliary malignancies arising from any site in the biliary tree, comprising 15% of all primary liver cancers. The nature of the disease and nonspecific presentation leads to late diagnosis and ultimately poor outcomes for patients. Combination gemcitabine and cisplatin has been the standard of care for cholangiocarcinoma (CCA) since 2010, with a median overall survival of 11.7 months. The five-year survival for CCA remains 5-10%, revealing a clear need for improved treatment options.

Methods: This targeted review highlights the role of next generation sequencing in CCA and the clinically relevant tumor biomarkers that have become the focus of therapeutic development.

Key content and findings: These tumor biomarkers or actionable mutations hold the potential to enable earlier diagnosis, provide prognostic information, and guide treatment decisions for patients with CCA. Specifically, the FGFR2 fusion and IDH1 mutation have shown considerable promise in development of targeted therapies. Clinical trials with inhibitors targeting FGFR2 fusion and IDH1 mutation have created expectations that these drugs will soon enter clinical practice. Other biomarkers including KRAS and B-raf protooncogenes, Her2/neu genes, and BRCA1 and 2 tumor-suppressor genes have also been touted as potential targets for future therapies, with early data showing promise for new drug development.

Conclusion: The discovery of these actionable mutations and identification of targeted therapies have challenged the notion of a "one-size fits all" for treatment of CCA, and generated optimism that these novel treatments will soon be available for patients with CCA.

Keywords: Cholangiocarcinoma (CCA); FGFR2 fusion; IDH; targeted therapies; tumor biomarkers.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-20-475/coif). SKM serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. RTS reports grants from Merck, non-financial support from Seattle Genetics, grants from Exelixis Pharmaceuticals, non-financial support from QED, non-financial support from Debiopharm, non-financial support from Agios, non-financial support from Clovis, grants from Haloyzme, grants from Pieris, grants from Taiho, non-financial support from Incyte, outside the submitted work. The other author has no conflicts of interest to declare.

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