1. Signalling networks in cholangiocarcinoma: Molecular pathogenesis, targeted therapies and drug resistance
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Majdi, Amine, Aoudjehane, Lynda, Ratziu, Vlad, Islam, Tawhidul, Conti, Filomena, Mestiri, Taïeb, Lagouge, Marie, Foufelle, Fabienne, Ballenghien, Florine, Ledent, Tatiana, Moldes, Marthe, Cadoret, Axelle, Delaunay, Jean-Louis, Aït-Slimane, Tounsia, Courtois, Gilles, Fève, Bruno, Scatton, Olivier, Prip-Buus, Carina, Rodrigues, Cecília M.P., Housset, Chantal, Gautheron, Jérémie, Fouassier, Laura, Marzioni, Marco, Afonso, Marta, Dooley, Steven, Gaston, Kevin, Giannelli, Gianluigi, Rodrigues, Cecilia, Lozano, Elisa, Mancarella, Serena, Segatto, Oreste, Vaquero, Javier, Marin, Jose, Coulouarn, Cédric, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade de Lisboa = University of Lisbon (ULISBOA), Heidelberg University, University of Nottingham, UK (UON), Universidad de Salamanca, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), LF and JV are funded by the LABEX Plas@par project and received financial state aid managed by the Agence Nationale de la Recherche, as part of the programme ‘Investissements d'avenir’ under the reference ANR-11-IDEX-0004-02. MM was funded by UNIVPM grant 040020_R.SCIENT.A_2018. CC is funded by Inserm, Univ Rennes, INCa and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (non-coding RNA in cancerology: fundamental to translational). KG is funded by the UK Medical Research Council (MR/N012615/1) and the Thailand Research Fund (TRF) (DBG5980005). CMPR and MBA are funded by COMPETE2020 and FCT (SAICTPAC/0019/2015 - LISBOA-01-0145-FEDER-016405), Portugal. OS is funded by AIRC (IG 16726). JJM is funded by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by the European Regional Development Fund/European Social Fund, ‘Investing in your future’), the Spanish Ministry of Economy, Industry and Competitiveness (SAF2016-75197-R), the Regional Government of Castile and Leon (SA063P17). The authors of this review article are members of the European Network for the Study of Cholangiocarcinoma and participate in the initiative COST Action EURO-CHOLANGIO-NET granted by the COST Association (CA18122) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E)., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), Human HepCell [AP-HP Hôpital Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP - Hôpital Saint-Antoine -Paris Biotech santé, Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de chirurgie digestive hépato-bilio-pancréatique transplantation hépatique [CHU Pitié-Salpêtrière], Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Trafic Membranaire et Signalisation Dans les Cellules Epitheliales, Centre de Mathématiques Laurent Schwartz (CMLS), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [APHP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry, University of Bristol [Bristol], Università degli studi di Bari, iMed.UL, University of Lisbon, ITACA, Universidad Politécnica de Valencia, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universidade de Lisboa (ULISBOA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
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Drug Resistance ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Computational biology ,Drug resistance ,Disease ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,Humans ,Medicine ,Molecular Targeted Therapy ,Epigenetics ,ComputingMilieux_MISCELLANEOUS ,Hepatology ,business.industry ,Molecular pathogenesis ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Therapeutic resistance ,3. Good health ,Bile Ducts, Intrahepatic ,Signalling ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Tumour stroma ,cardiovascular system ,030211 gastroenterology & hepatology ,business ,Signal Transduction - Abstract
Special Issue: Cholangiocarcinoma; International audience; Cholangiocarcinoma (CCA) is a deadly disease. While surgery may attain cure in a minor fraction of cases, therapeutic options in either the adjuvant or advanced setting are limited. The possibility of advancing the efficacy of therapeutic approaches to CCA relies on understanding its molecular pathogenesis and developing rational therapies aimed at interfering with oncogenic signalling networks that drive and sustain cholangiocarcinogenesis. These efforts are complicated by the intricate biology of CCA, which integrates not only the driving force of tumour cell-intrinsic alterations at the genetic and epigenetic level but also pro-tumorigenic cues conveyed to CCA cells by different cell types present in the rich tumour stroma. Herein, we review our current understanding of the mechanistic bases underpinning the activation of major oncogenic pathways causative of CCA pathogenesis. We subsequently discuss how this knowledge is being exploited to implement rationale-based and genotype-matched therapeutic approaches that predictably will radically transform CCA clinical management in the next decade. We conclude by highlighting the mechanisms of therapeutic resistance in CCA and reviewing innovative approaches to combat resistance at the preclinical and clinical level.
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- 2019
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