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...
| Authors: | ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2023 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10459.1/464443 |
| Online Access: | https://doi.org/10.20517/2394-5079.2023.04 https://hdl.handle.net/10459.1/464443 |
| Access Level: | Open access |
| Keyword: | Biliary tract cancer Extrahepatic cholangiocarcinoma Genetic alterations Molecular classification Targeted therapies Biomarkers |
| _version_ | 1878739985407934465 |
|---|---|
| author | Oronich, Arnau |
| author2 | Pallisé, Ona Salud Salvia, Maria Antonieta Montal Roura, Robert |
| author2_role | author author author |
| author_browse | Montal Roura, Robert Oronich, Arnau Pallisé, Ona Salud Salvia, Maria Antonieta |
| author_facet | Oronich, Arnau Pallisé, Ona Salud Salvia, Maria Antonieta Montal Roura, Robert |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_cba01b4e42e53a5d95176c97cb698eda |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10459.1/464443 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | OAE Publishing |
| publisherStr | OAE Publishing |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma Oronich, Arnau Pallisé, Ona Salud Salvia, Maria Antonieta Montal Roura, Robert Biliary tract cancer Extrahepatic cholangiocarcinoma Genetic alterations Molecular classification Targeted therapies Biomarkers 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. OAE Publishing https://doi.org/10.20517/2394-5079.2023.04 https://hdl.handle.net/10459.1/464443 |
| spellingShingle | Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma Oronich, Arnau Biliary tract cancer Extrahepatic cholangiocarcinoma Genetic alterations Molecular classification Targeted therapies Biomarkers |
| status_str | publishedVersion |
| title | 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_short | Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma |
| title_sort | Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma |
| topic | Biliary tract cancer Extrahepatic cholangiocarcinoma Genetic alterations Molecular classification Targeted therapies Biomarkers |
| topic_facet | Biliary tract cancer Extrahepatic cholangiocarcinoma Genetic alterations Molecular classification Targeted therapies Biomarkers |
| url | https://doi.org/10.20517/2394-5079.2023.04 https://hdl.handle.net/10459.1/464443 |