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...
| Autores: | , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Recursos: | Universitat de Lleida (UdL) |
| Repositorio: | Repositori Obert UdL |
| OAI Identifier: | oai:repositori.udl.cat:10459.1/464443 |
| Acesso em linha: | https://doi.org/10.20517/2394-5079.2023.04 https://hdl.handle.net/10459.1/464443 |
| Access Level: | acceso abierto |
| Palavra-chave: | Biliary tract cancer Extrahepatic cholangiocarcinoma Genetic alterations Molecular classification Targeted therapies Biomarkers |
| Resumo: | 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. |
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