Cholangiocarcinoma 2020: the next horizon in mechanisms and management.

Jesus M Banales, Jose J G Marin, Angela Lamarca, Pedro M Rodrigues, Shahid A Khan, Lewis R Roberts, Vincenzo Cardinale, Guido Carpino, Jesper B Andersen, Chiara Braconi, Diego F Calvisi, Maria J Perugorria, Luca Fabris, Luke Boulter, Rocio I R Macias, Eugenio Gaudio, Domenico Alvaro, Sergio A Gradilone, Mario Strazzabosco, Marco Marzioni, Cédric Coulouarn, Laura Fouassier, Chiara Raggi, Pietro Invernizzi, Joachim C Mertens, Anja Moncsek, Sumera I. Ilyas, Julie Heimbach, Bas Groot Koerkamp, Jordi Bruix, Alejandro Forner, John Bridgewater, Juan W Valle, Gregory J Gores

Journal: Nature reviews. Gastroenterology & hepatology 2020;17(9):557-588

PMID: 32606456

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Abstract

Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.

Address: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain. [email protected].; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain. [email protected].; Ikerbasque, Basque Foundation for Science, Bilbao, Spain. [email protected].; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain.; Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain.; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.; Division of Cancer Sciences, University of Manchester, Manchester, UK.; Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.; Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.; Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, Italy.; Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.; Institute of Pathology, University of Regensburg, Regensburg, Germany.; Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain.; Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy.; Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA.; MRC-Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.; Division of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.; Department of Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.; The Hormel Institute, University of Minnesota, Austin, MN, USA.; Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy.; INSERM, Université de Rennes, Rennes, France.; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France.; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.; Division of Gastroenterology and Center of Autoimmune Liver Diseases, Department of Medicine and Surgery, San Gerardo Hospital, University of Milano, Bicocca, Italy.; Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zürich, Switzerland.; Department of Surgery, Mayo Clinic, Rochester, MN, USA.; Department of Surgery, Erasmus Medical Center, Rotterdam, Netherlands.; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain.; Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Barcelona, Spain.; Department of Medical Oncology, UCL Cancer Institute, London, UK.

DOI: 10.1038/s41575-020-0310-z