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Review
. 2022 Jun;7(3):100505.
doi: 10.1016/j.esmoop.2022.100505. Epub 2022 Jun 10.

Role of molecular genetics in the clinical management of cholangiocarcinoma

N Normanno  1 , E Martinelli  2 , D Melisi  3 , C Pinto  4 , L Rimassa  5 , D Santini  6 , A Scarpa  7
Affiliations
Review

Role of molecular genetics in the clinical management of cholangiocarcinoma

N Normanno et al. ESMO Open. 2022 Jun.

Abstract

The incidence of cholangiocarcinoma (CCA) has steadily increased during the past 20 years, and mortality is increasing. The majority of patients with CCA have advanced or metastatic disease at diagnosis, and treatment options for unresectable disease are limited, resulting in poor prognosis. However, recent identification of targetable genomic alterations has expanded treatment options for eligible patients. Given the importance of early and accurate diagnosis in optimizing patient outcomes, this review discusses best practices in CCA diagnosis, with a focus on categorizing molecular genetics and available targeted therapies. Imaging and staging of CCAs are discussed, as well as recommended biopsy collection techniques, and molecular and genomic profiling methodologies, which have become increasingly important as molecular biomarker data accumulate. Approved agents targeting actionable genomic alterations specifically in patients with CCA include ivosidenib for tumors harboring IDH1 mutations, and infigratinib and pemigatinib for those with FGFR2 fusions. Other agents currently under development in this indication have shown promising results, which are presented here.

Keywords: FGFR2; IDH1; extrahepatic cholangiocarcinoma; genomic profile; intrahepatic cholangiocarcinoma.

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Conflict of interest statement

Disclosure NN received speaker’s fees and/or fees for advisory boards from MSD, Qiagen, Biocartis, Illumina, Incyte, Roche, Merck, Thermo Fisher, AstraZeneca, and Eli Lilly and research grants from Merck, Thermo Fisher, QIAGEN, Roche, Biocartis, and Illumina. LR has received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Zymeworks. CP has received personal fees for an advisory role, speaker engagements, and travel and accommodation expenses from Amgen, Astellas, AstraZeneca, Bayer, Bristol Meyer Squibb, Clovis Oncology, Ipsen, Janssen, Incyte, Merck-Serono, Merck Sharp and Dohme, Novartis, Roche, and Sanofi. EM has received honoraria or consultation fees for speaker, consultancy, or advisory roles from Amgen, Bayer, Eisai, Merck Serono, Pierre Fabre, Roche, Servier, and Incyte. DM has received research funding from Shire, Incyte, Evotec, Celgene, and iOnctura and consulting fees from Eli Lilly, Shire, Evotec, Baxter, Incyte, and iOnctura. DS has received consulting fees from Novartis, Incyte, BMS, MSD, Astellas, Jansen, Ipsen, Lilly, Sanofi, Eisai, and AstraZeneca. AS has received consulting fees from Amgen, AstraZeneca, Basilea, Incyte, and Ipsen and lecture fees from Amgen, Incyte, Ipsen, Merck Serono, Roche, and Sanofi.

Figures

Figure 1
Figure 1
Signs and symptoms of cholangiocarcinoma.aBiliary obstruction can occur from tumors in the major bile ducts (perihilar cholangiocarcinoma or distal cholangiocarcinoma), or because of lymph node compression at the hilum. Reprinted from Valle et al., with permission from Elsevier.
Figure 2
Figure 2
Common genetic alterations in intrahepatic and extrahepatic cholangiocarcinoma (CCA)., , , , Genetic alterations in red can be targeted by available therapies.
See this image and copyright information in PMC

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