PMID- 35696744 OWN - NLM STAT- MEDLINE DCOM- 20220711 LR - 20230916 IS - 2059-7029 (Electronic) IS - 2059-7029 (Linking) VI - 7 IP - 3 DP - 2022 Jun TI - Role of molecular genetics in the clinical management of cholangiocarcinoma. PG - 100505 LID - S2059-7029(22)00125-9 [pii] LID - 10.1016/j.esmoop.2022.100505 [doi] LID - 100505 AB - 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. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Normanno, N AU - Normanno N AD - Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale-IRCCS, Naples, Italy. Electronic address: n.normanno@istitutotumori.na.it. FAU - Martinelli, E AU - Martinelli E AD - Medical Oncology, Department of Precision Medicine, Universita della Campania 'L. Vanvitelli', Naples, Italy. FAU - Melisi, D AU - Melisi D AD - Investigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Digestive Molecular Clinical Oncology Research Unit, University of Verona, Policlinico B.B. Rossi, Verona, Italy. FAU - Pinto, C AU - Pinto C AD - Medical Oncology Unit, Comprehensive Cancer Centre, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. FAU - Rimassa, L AU - Rimassa L AD - Department of Biomedical Sciences, Humanitas University, Milan, Italy; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy. FAU - Santini, D AU - Santini D AD - Medical Oncology, University Campus Bio-Medico, Rome, Italy. FAU - Scarpa, A AU - Scarpa A AD - ARC-Net Research Centre and Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Policlinico G.B. Rossi, Verona, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20220610 PL - England TA - ESMO Open JT - ESMO open JID - 101690685 SB - IM MH - *Bile Duct Neoplasms/drug therapy/genetics/pathology MH - Bile Ducts, Intrahepatic/pathology MH - *Cholangiocarcinoma/drug therapy/genetics/pathology MH - Humans MH - Molecular Biology PMC - PMC9198375 OTO - NOTNLM OT - FGFR2 OT - IDH1 OT - extrahepatic cholangiocarcinoma OT - genomic profile OT - intrahepatic cholangiocarcinoma COIS- 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. EDAT- 2022/06/14 06:00 MHDA- 2022/07/12 06:00 PMCR- 2022/06/10 CRDT- 2022/06/13 18:03 PHST- 2022/03/30 00:00 [received] PHST- 2022/05/05 00:00 [revised] PHST- 2022/05/07 00:00 [accepted] PHST- 2022/06/14 06:00 [pubmed] PHST- 2022/07/12 06:00 [medline] PHST- 2022/06/13 18:03 [entrez] PHST- 2022/06/10 00:00 [pmc-release] AID - S2059-7029(22)00125-9 [pii] AID - 100505 [pii] AID - 10.1016/j.esmoop.2022.100505 [doi] PST - ppublish SO - ESMO Open. 2022 Jun;7(3):100505. doi: 10.1016/j.esmoop.2022.100505. Epub 2022 Jun 10.