Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma

The global morbimortality of biliary tract cancer (BTC) is steadily increasing and accounts for ~10% of all primary liver cancer. Distinct anatomical locations of BTC have singularities in their etiopathogenesis, which are translated into differences in their molecular fingerprints and the associate...

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Autores: Oronich, Arnau, Pallisé, Ona, Salud Salvia, Maria Antonieta, Montal Roura, Robert
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/464443
Acceso en línea:https://doi.org/10.20517/2394-5079.2023.04
https://hdl.handle.net/10459.1/464443
Access Level:acceso abierto
Palabra clave:Biliary tract cancer
Extrahepatic cholangiocarcinoma
Genetic alterations
Molecular classification
Targeted therapies
Biomarkers
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spelling Genomic alterations and targeted therapies in extrahepatic cholangiocarcinomaOronich, ArnauPallisé, OnaSalud Salvia, Maria AntonietaMontal Roura, RobertBiliary tract cancerExtrahepatic cholangiocarcinomaGenetic alterationsMolecular classificationTargeted therapiesBiomarkersThe global morbimortality of biliary tract cancer (BTC) is steadily increasing and accounts for ~10% of all primary liver cancer. Distinct anatomical locations of BTC have singularities in their etiopathogenesis, which are translated into differences in their molecular fingerprints and the associated therapeutic approaches. Extrahepatic cholangiocarcinoma (eCCA), arising in the large and distal bile ducts, presents recurrent activating mutations of KRAS and loss-of-function alterations in TP53, SMAD4, and CDKN2A/B. Despite being highly prevalent, no targeted therapies are yet available for these oncogenic drivers. ERBB2 mutations and amplifications, on the other hand, are the most recurrent actionable alterations for eCCA, with several clinical trials aiming to provide benefits in biomarker-enriched populations. In addition, integrative multi-omics analysis of eCCA has allowed the identification of novel molecular classes of this disease that could be therapeutically exploited. Beyond that, the highly immunosuppressive tumor microenvironment of eCCA has prevented until now the success of immune checkpoint inhibitors, recently approved in combination with cytotoxic chemotherapy. Further characterization of eCCA at the molecular level would potentially foster treating patients based on a precision oncology approach in order to increase the clinical outcomes for this challenging disease.OAE Publishing2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.20517/2394-5079.2023.04https://hdl.handle.net/10459.1/464443reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a https://doi.org/10.20517/2394-5079.2023.04Hepatoma Research, 2023, vol. 9, 26cc-by (c) Arnau Oronich et al., 2023Attribution 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:recercat.cat:10459.1/4644432026-05-29T05:05:01Z
dc.title.none.fl_str_mv Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
title Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
spellingShingle Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
Oronich, Arnau
Biliary tract cancer
Extrahepatic cholangiocarcinoma
Genetic alterations
Molecular classification
Targeted therapies
Biomarkers
title_short Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
title_full Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
title_fullStr Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
title_full_unstemmed Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
title_sort Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma
dc.creator.none.fl_str_mv Oronich, Arnau
Pallisé, Ona
Salud Salvia, Maria Antonieta
Montal Roura, Robert
author Oronich, Arnau
author_facet Oronich, Arnau
Pallisé, Ona
Salud Salvia, Maria Antonieta
Montal Roura, Robert
author_role author
author2 Pallisé, Ona
Salud Salvia, Maria Antonieta
Montal Roura, Robert
author2_role author
author
author
dc.subject.none.fl_str_mv Biliary tract cancer
Extrahepatic cholangiocarcinoma
Genetic alterations
Molecular classification
Targeted therapies
Biomarkers
topic Biliary tract cancer
Extrahepatic cholangiocarcinoma
Genetic alterations
Molecular classification
Targeted therapies
Biomarkers
description The global morbimortality of biliary tract cancer (BTC) is steadily increasing and accounts for ~10% of all primary liver cancer. Distinct anatomical locations of BTC have singularities in their etiopathogenesis, which are translated into differences in their molecular fingerprints and the associated therapeutic approaches. Extrahepatic cholangiocarcinoma (eCCA), arising in the large and distal bile ducts, presents recurrent activating mutations of KRAS and loss-of-function alterations in TP53, SMAD4, and CDKN2A/B. Despite being highly prevalent, no targeted therapies are yet available for these oncogenic drivers. ERBB2 mutations and amplifications, on the other hand, are the most recurrent actionable alterations for eCCA, with several clinical trials aiming to provide benefits in biomarker-enriched populations. In addition, integrative multi-omics analysis of eCCA has allowed the identification of novel molecular classes of this disease that could be therapeutically exploited. Beyond that, the highly immunosuppressive tumor microenvironment of eCCA has prevented until now the success of immune checkpoint inhibitors, recently approved in combination with cytotoxic chemotherapy. Further characterization of eCCA at the molecular level would potentially foster treating patients based on a precision oncology approach in order to increase the clinical outcomes for this challenging disease.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.20517/2394-5079.2023.04
https://hdl.handle.net/10459.1/464443
url https://doi.org/10.20517/2394-5079.2023.04
https://hdl.handle.net/10459.1/464443
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a https://doi.org/10.20517/2394-5079.2023.04
Hepatoma Research, 2023, vol. 9, 26
dc.rights.none.fl_str_mv cc-by (c) Arnau Oronich et al., 2023
Attribution 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c) Arnau Oronich et al., 2023
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv OAE Publishing
publisher.none.fl_str_mv OAE Publishing
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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