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
Marta B. Afonso
Professor KEVIN GASTON Kevin.Gaston@nottingham.ac.uk
Professor of Cancer Studies
Cecilia M. P. Rodrigues
Jose J. G. Marin
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|
|Peer Reviewed||Peer Reviewed|
|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|
|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
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