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Review
. 2022 Mar 31;14(7):1789.
doi: 10.3390/cancers14071789.

Targeted Therapies for Perihilar Cholangiocarcinoma

Simon Gray  1 , Angela Lamarca  1   2 , Julien Edeline  3 , Heinz-Josef Klümpen  4 , Richard A Hubner  1   2 , Mairéad G McNamara  1   2 , Juan W Valle  1   2
Affiliations
Review

Targeted Therapies for Perihilar Cholangiocarcinoma

Simon Gray et al. Cancers (Basel). .

Abstract

Perihilar cholangiocarcinoma (pCCA) is the anatomical sub-group of biliary tract cancer (BTC) arising between the second-order intrahepatic bile ducts and the cystic duct. Together with distal and intrahepatic cholangiocarcinoma (dCCA and iCCA; originating distal to, and proximal to this, respectively), gallbladder cancer (GBC) and ampulla of Vater carcinoma (AVC), these clinicopathologically and molecularly distinct entities comprise biliary tract cancer (BTC). Most pCCAs are unresectable at diagnosis, and for those with resectable disease, surgery is extensive, and recurrence is common. Therefore, the majority of patients with pCCA will require systemic treatment for advanced disease. The prognosis with cytotoxic chemotherapy remains poor, driving interest in therapies targeted to the molecular nature of a given patient's cancer. In recent years, the search for efficacious targeted therapies has been fuelled both by whole-genome and epigenomic studies, looking to uncover the molecular landscape of CCA, and by specifically testing for aberrations where established therapies exist in other indications. This review aims to provide a focus on the current molecular characterisation of pCCA, targeted therapies applicable to pCCA, and future directions in applying personalised medicine to this difficult-to-treat malignancy.

Keywords: biliary tract cancer; cholangiocarcinoma; extrahepatic; pCCA; perihilar; targeted therapy.

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Conflict of interest statement

S.G. has no conflicts of interest to declare. A.L. has received travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan and Delcath; speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA, QED and Servier; advisory honoraria from EISAI, Nutricia Ipsen, QED, Roche and Servier; she is a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. J.E. has received honoraria from MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier and Beigene. He has received travel support from Amgen. He has received research funding (institutional) from BMS and Beigene. H.-J.K. has had consulting or advisory roles for Janssen and Astra Zeneca; speakers’ bureau for Medtalk and Ipsen. He has received research funding (institutional) from ITM Solucin, MSD, BAYER, INCYTE, Taiho, Roche and IPSEN. R.H. has served on the advisory boards for Roche, BMS, Eisai, Celgene, Beigene, Ipsen and BTG. He has received speaker fees from Eisai, Ipsen, Mylan, PrimeOncology and has received travel and educational support from Bayer, BMS and Roche. M.G.M. has received research grant support from Servier, Ipsen and NuCana. She has received travel and accommodation support from Bayer and Ipsen, and speaker honoraria from Advanced Accelerator Applications (UK and Ireland) Ltd., Pfizer, Ipsen, NuCana and Mylan. She has served on advisory boards for Celgene, Ipsen, Sirtex, Baxalta and Incyte. J.W.V. has had consulting or advisory roles for Agios, AstraZeneca, Delcath Systems, Keocyt, Genoscience Pharma, Incyte, Ipsen, Merck, Mundipharma EDO, Novartis, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED and Wren Laboratories; is on speakers’ bureaus for Imaging Equipment Limited, Ipsen, Novartis and Nucana; and has received travel grants from Celgene and Nucana.

Figures

Figure 1
Figure 1
Frequency of potentially actionable molecular aberrations in perihilar cholangiocarcinoma. Anatomical groupings of patients sampled to determine each frequency are beside/below the corresponding frequency [25,26,27,28,29,30,31,32,33,34,35,36]. Rates of co-occurrence of the described molecular aberrations within patients are unknown. Created with BioRender.com. KRAS, Kirsten rat sarcoma virus. eCCA, extrahepatic cholangiocarcinoma. HRD, homologous repair deficiency. BRCA, breast cancer susceptibility gene. BTC, biliary tract cancer. HER2, human epidermal growth factor receptor 2. BRAF, v-Raf murine sarcoma viral oncogene homolog B. EGFR, epidermal growth factor receptor. MSI-H, microsatellite instability high. pCCA, perihilar cholangiocarcinoma. IDH, isocitrate dehydrogenase. NTRK, neurotrophic tropomyosin receptor kinases. FGFR2, fibroblast growth factor receptor 2.
See this image and copyright information in PMC

References

    1. Valle J.W., Kelley R.K., Nervi B., Oh D.-Y., Zhu A.X. Biliary tract cancer. Lancet. 2021;397:428–444. doi: 10.1016/S0140-6736(21)00153-7. - DOI - PubMed
    1. Banales J.M., Marin J.J.G., Lamarca A., Rodrigues P.M., Khan S.A., Roberts L.R., Cardinale V., Carpino G., Andersen J.B., Braconi C., et al. Cholangiocarcinoma 2020: The next horizon in mechanisms and management. Nat. Rev. Gastroenterol. Hepatol. 2020;17:557–588. doi: 10.1038/s41575-020-0310-z. - DOI - PMC - PubMed
    1. Brunt E., Aishima S., Clavien P.-A., Fowler K., Goodman Z., Gores G., Gouw A., Kagen A., Klimstra D., Komuta M., et al. cHCC-CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation. Hepatology. 2018;68:113–126. doi: 10.1002/hep.29789. - DOI - PMC - PubMed
    1. Rizvi S., Gores G.J. Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma. Gastroenterology. 2013;145:1215–1229. doi: 10.1053/j.gastro.2013.10.013. - DOI - PMC - PubMed
    1. Groot Koerkamp B., Wiggers J.K., Allen P.J., Besselink M.G., Blumgart L.H., Busch O.R., Coelen R., D’Angelica M.I., DeMatteo R.P., Gouma D.J., et al. Recurrence Rate and Pattern of Perihilar Cholangiocarcinoma after Curative Intent Resection. J. Am. Coll. Surg. 2015;221:1041–1049. doi: 10.1016/j.jamcollsurg.2015.09.005. - DOI - PMC - PubMed

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