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Signaling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance

Fouassier, Laura; Marzioni, Marco; Afonso, Marta B.; Dooley, Steven; Gaston, Kevin; Giannelli, Gianluigi; Rodrigues, Cecilia M. P.; Lozano, Elisa; Mancarella, Serena; Segatto, Oreste; Vaquero, Javier; Marin, Jose J. G.; Coulouarn, Cédric

Authors

Laura Fouassier

Marco Marzioni

Marta B. Afonso

Steven Dooley

Gianluigi Giannelli

Cecilia M. P. Rodrigues

Elisa Lozano

Serena Mancarella

Oreste Segatto

Javier Vaquero

Jose J. G. Marin

Cédric Coulouarn



Abstract

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 signaling networks that drive and sustain cholangiocarcinogenesis. These efforts are complicated by the intricate biology of CCA, which integrates not only the driving force of tumor‐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 tumor 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 mechanisms of therapeutic resistance in CCA and reviewing innovative approaches to combat resistance at the pre‐clinical and clinical level.

Journal Article Type Article
Publication Date Mar 23, 2019
Journal Liver International
Print ISSN 1478-3223
Electronic ISSN 1478-3231
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 39
Issue S1
Pages 43-62
APA6 Citation Fouassier, L., Marzioni, M., Afonso, M. B., Dooley, S., Gaston, K., Giannelli, G., …Coulouarn, C. (2019). Signaling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance. Liver International, 39(S1), 43-62. https://doi.org/10.1111/liv.14102
DOI https://doi.org/10.1111/liv.14102
Keywords Hepatology
Publisher URL https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.14102
Additional Information This is the peer reviewed version of the following article: Fouassier, L. , Marzioni, M. , Afonso, M. B., Dooley, S. , Gaston, K. , Giannelli, G. , Rodrigues, C. M., Lozano, E. , Mancarella, S. , Segatto, O. , Vaquero, J. , Marin, J. J. and Coulouarn, C. (2019), Signaling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance. Liver Int which has been published in final form at https://doi.org/10.1111/liv.14102
. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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