Signalling networks in cholangiocarcinoma

Molecular pathogenesis, targeted therapies and drug resistance

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

Research output: Contribution to journalReview article

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 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.

Original languageEnglish
Pages (from-to)43-62
Number of pages20
JournalLiver International
Volume39 Suppl 1
DOIs
Publication statusPublished - May 2019

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Molecular Targeted Therapy
Cholangiocarcinoma
Drug Resistance
Therapeutics
Epigenomics
Cues
Neoplasms
Genotype

Cite this

Fouassier, L., Marzioni, M., Afonso, M. B., Dooley, S., Gaston, K., Giannelli, G., ... Coulouarn, C. (2019). Signalling networks in cholangiocarcinoma: Molecular pathogenesis, targeted therapies and drug resistance. Liver International, 39 Suppl 1, 43-62. https://doi.org/10.1111/liv.14102

Signalling 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.

In: Liver International, Vol. 39 Suppl 1, 05.2019, p. 43-62.

Research output: Contribution to journalReview article

Fouassier, L, Marzioni, M, Afonso, MB, Dooley, S, Gaston, K, Giannelli, G, Rodrigues, CMP, Lozano, E, Mancarella, S, Segatto, O, Vaquero, J, Marin, JJG & Coulouarn, C 2019, 'Signalling networks in cholangiocarcinoma: Molecular pathogenesis, targeted therapies and drug resistance', Liver International, vol. 39 Suppl 1, pp. 43-62. https://doi.org/10.1111/liv.14102
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. / Signalling networks in cholangiocarcinoma : Molecular pathogenesis, targeted therapies and drug resistance. In: Liver International. 2019 ; Vol. 39 Suppl 1. pp. 43-62.
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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 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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T2 - Molecular pathogenesis, targeted therapies and drug resistance

AU - Fouassier, Laura

AU - Marzioni, Marco

AU - Afonso, Marta B

AU - Dooley, Steven

AU - Gaston, Kevin

AU - Giannelli, Gianluigi

AU - Rodrigues, Cecilia M P

AU - Lozano, Elisa

AU - Mancarella, Serena

AU - Segatto, Oreste

AU - Vaquero, Javier

AU - Marin, Jose J G

AU - Coulouarn, Cédric

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N2 - 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.

AB - 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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DO - 10.1111/liv.14102

M3 - Review article

VL - 39 Suppl 1

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SN - 1478-3223

ER -