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Current and novel therapeutic opportunities for systemic therapy in biliary cancer

British Journal of Cancer volume 123, pages 1047–1059 (2020)Cite this article

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A Correction to this article was published on 05 July 2021

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Abstract

Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools.

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Fig. 1: Schematic representation of the molecular mechanisms of chemoresistance, of which there are seven depicted.56,57

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Acknowledgements

This work was performed under the frame of Working Group 6 of the COST Action collaboration (COST Action CA18122 European Cholangiocarcinoma Network, EURO-CHOLANGIO-NET).

Author information

Authors and Affiliations

  1. IBSAL, University of Salamanca, Salamanca, Spain

    José J. G. Marin & Rocío I. R. Macias

  2. National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Health Institute, Madrid, ES, Spain

    José J. G. Marin, Rocío I. R. Macias & Jesus M. Banales

  3. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK

    Maria Giuseppina Prete & Chiara Braconi

  4. Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center - IRCCS -, Rozzano (MI), Italy

    Maria Giuseppina Prete

  5. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK

    Angela Lamarca & Juan W. Valle

  6. Division of Cancer Sciences, University of Manchester, Manchester, UK

    Angela Lamarca & Juan W. Valle

  7. Medical Oncology Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy

    Simona Tavolari

  8. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain

    Ana Landa-Magdalena, Pedro M. Rodrigues, Adelaida La Casta & Jesus M. Banales

  9. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum-University of Bologna, Bologna, Italy

    Giovanni Brandi

  10. Unit of Oncogenomics and Epigenetics, IRCCS Regina Elena National Cancer Institute, Rome, Italy

    Oreste Segatto

  11. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany

    Arndt Vogel

  12. Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland

    Joachim Mertens

  13. Research Insitute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

    Cecilia M. P. Rodrigues

  14. CIMA, University of Navarra, IdisNA, Navarra, Spain

    Maite G. Fernandez-Barrena

  15. Coimbra Hospital and University Centre (CHUC), Coimbra, Portugal

    Ana Da Silva Ruivo

  16. Università Politecnica delle Marche/Ospedali Riuniti di Ancona, Ancona, Italy

    Marco Marzioni & Giulia Mentrasti

  17. Institute for Liver and Digestive Health, University College London, London, UK

    Pilar Acedo

  18. Biotech Research & Innovation Centre (BRIC), University of Copenhaghen, Copenhagen, Denmark

    Patricia Munoz-Garrido

  19. La Sapienza University, Rome, Italy

    Vincenzo Cardinale

  20. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

    Jesus M. Banales

  21. UCL Cancer Institute, London, UK

    John Bridgewater

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  1. José J. G. Marin
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  2. Maria Giuseppina Prete
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  3. Angela Lamarca
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Consortia

on behalf of the working group 6 of the COST-action 18122 (Euro-Cholangio-NET) as part of the European Network for the study of Cholangiocarcinoma (ENSCCA)

Contributions

C.B., J.J.G.M., M.G.P., A.L., S.T., A.L.M., G.B., O.S., A.V., R.I.R.M., P.M.R., A.C., M.J., C.M.P.R., M.G.F.-B., A.S.R., M.M., G.M., P.A., P.M.G., V.C., J.M.B., J.W.V. and J.B. contributed to the writing and the review of the paper. All authors approved the final version of the paper.

Corresponding author

Correspondence to Chiara Braconi.

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Competing interests

The authors declare the following competing interest: C.B. and/or her family members received speaker honoraria from Bayer, EliLilly, Pfizer and Merck-Serono. A.L.M. received travel funding from Pfizer, Merck, Roche and Lilly. A.L. received travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan and Delcath; speaker honoraria from Merck, Pfizer, Ipsen, Incyte and AAA; advisory honoraria from EISAI, Nutricia Ipsen, QED and Roche; she is also a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. A.V. received honoraria form Meck, MSD, BMS, INCYTE, AstraZeneca, Roche, Bayer, Basilea, BTG, Novartis and Decath. J.W.V. received honoraria from Agios, AstraZeneca, Debiopharm, Delcath Systems, GenoScience Pharma, Imaging Equipment Ltd, Incyte, Ipsen, Keocyt, Merck, Mundipharma EDO, Novartis, Nucana, PCI Biotech, Pieris Pharmaceuticals, Pfizer, QED, Servier and Wren Laboratories, and declares Speakers’ Bureau for Imaging Equipment Ltd, Ipsen, Novartis and Nucana.

Funding information

C.B. LKAS readership—University of Glasgow: J.J.G.M./R.I.R.M. Carlos III Institute of Health, Spain (PI16/00598); “Centro Internacional sobre el Envejecimiento”, Spain (OLD-HEPAMARKER, 0348-CIE-6-E); C.M.P.R. is supported by FEDER funds through the COMPETE programme and by national funds through Fundação para a Ciência e a Tecnologia (grants PTDC/MED-FAR/29097/2017 and SAICTPAC/0019/2015—LISBOA-01-0145-FEDER-016405). A.L. was part-funded by The Christie Charity. MGF-B is supported by grants SAF2014-54191-R and SAF2017-88933-R from FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación; HEPACARE Project from Fundación La Caixa. J.M.B. was funded by Spanish Carlos III Health Institute (ISCIII) (FIS PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129), cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); AMMF (J.M. Banales and P.M. Rodrigues 2019/202); PSC Partners US; PSC Supports UK (06119JB); Horizon 2020 (H2020 ESCALON project: H2020-SC1-BHC-2018-2020); IKERBASQUE, Basque foundation for Science; CIBERehd (ISCIII); “Diputación Foral Gipuzkoa” (DFG15/010, DFG16/004), BIOEF (Basque Foundation for Innovation and Health Research); EiTB Maratoia (BIO15/CA/016/BD); Department of Health of the Basque Country (2017111010) and Euskadi RIS3 (2016222001, 2017222014, 2018222029 and 2019222054); La Caixa Scientific Foundation (HR17-00601); “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to J.M. Banales and J.J.G. Marin). P.M.R. was funded by Spanish Carlos III Health Institute (ISCIII; Sara Borrell CD19/00254) cofinanced by “Fondo Europeo de Desarrollo Regional”. M.M. received PSA-2017-UNIVPM. P.A. is supported by a NIHR-Biomedical Research Centre funding (BRC646b/III/SP/101350). O.S. is funded by AIRC (IG2018, ID 21627, PI Segatto Oreste). A.V. is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - SFB/TRR 209 - 314905040, and Vo959/9-1. This work was performed under the frame of Working Group 6 of the COST Action CA18122 European Cholangiocarcinoma Network supported by COST (European Cooperation in Science and Technology) http://www.cost.eu.

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Marin, J.J.G., Prete, M.G., Lamarca, A. et al. Current and novel therapeutic opportunities for systemic therapy in biliary cancer. Br J Cancer 123, 1047–1059 (2020). https://doi.org/10.1038/s41416-020-0987-3

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