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Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers

SIMPLE SUMMARY: Biliary tract cancers (BTC) include gallbladder cancers, intrahepatic, perihilar and distal extrahepatic cholangiocarcinomas. BTCs represent a major health problem due to their increasing global incidence and associated poor prognosis. The majority of patients present with advanced s...

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Autores principales: Kang, Sandra, El-Rayes, Bassel F., Akce, Mehmet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996885/
https://www.ncbi.nlm.nih.gov/pubmed/35406520
http://dx.doi.org/10.3390/cancers14071748
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author Kang, Sandra
El-Rayes, Bassel F.
Akce, Mehmet
author_facet Kang, Sandra
El-Rayes, Bassel F.
Akce, Mehmet
author_sort Kang, Sandra
collection PubMed
description SIMPLE SUMMARY: Biliary tract cancers (BTC) include gallbladder cancers, intrahepatic, perihilar and distal extrahepatic cholangiocarcinomas. BTCs represent a major health problem due to their increasing global incidence and associated poor prognosis. The majority of patients present with advanced stages of cancer, where cytotoxic chemotherapy provides modest survival benefit. More recently, novel treatment options have emerged with the development of agents targeting specific genetic mutations of tumors as well as immunotherapy, which enhances the immune system’s ability to target cancer cells efficiently. In this review, we will discuss current and emerging systemic therapy options and the rationale for immunotherapy in BTC. ABSTRACT: Biliary tract cancers (BTC) comprise a rare and diverse group of malignancies that involve the gallbladder and biliary tree. These cancers typically present in later stages because they are aggressive in nature and affected patients are often asymptomatic in earlier stages of disease. Moreover, BTCs are generally refractory to cytotoxic chemotherapy, which further contributes to their associated poor survival outcomes. Novel therapy approaches are clearly needed. Molecular targeted agents have been developed based on our expanding knowledge of the genetic mutations underlying BTCs and represent a promising treatment strategy in molecularly selected subgroups of patients. In addition, the advent of immunotherapy over recent years has dramatically changed the bleak outcomes observed in malignancies such as melanoma. Our growing understanding of the complex tumor microenvironment in BTC has identified mechanisms of tumor immune evasion that could potentially be targeted with immunotherapy. As a result, different immunotherapeutic approaches including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, have been investigated. The use of immunotherapeutic agents is currently only approved for a small subset of treatment-refractory BTCs based on microsatellite instability (MSI) status and tumor mutational burden (TMB), but this will likely change with the potential approval of immunotherapy plus chemotherapy as a result of the TOPAZ-1 trial.
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spelling pubmed-89968852022-04-12 Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers Kang, Sandra El-Rayes, Bassel F. Akce, Mehmet Cancers (Basel) Review SIMPLE SUMMARY: Biliary tract cancers (BTC) include gallbladder cancers, intrahepatic, perihilar and distal extrahepatic cholangiocarcinomas. BTCs represent a major health problem due to their increasing global incidence and associated poor prognosis. The majority of patients present with advanced stages of cancer, where cytotoxic chemotherapy provides modest survival benefit. More recently, novel treatment options have emerged with the development of agents targeting specific genetic mutations of tumors as well as immunotherapy, which enhances the immune system’s ability to target cancer cells efficiently. In this review, we will discuss current and emerging systemic therapy options and the rationale for immunotherapy in BTC. ABSTRACT: Biliary tract cancers (BTC) comprise a rare and diverse group of malignancies that involve the gallbladder and biliary tree. These cancers typically present in later stages because they are aggressive in nature and affected patients are often asymptomatic in earlier stages of disease. Moreover, BTCs are generally refractory to cytotoxic chemotherapy, which further contributes to their associated poor survival outcomes. Novel therapy approaches are clearly needed. Molecular targeted agents have been developed based on our expanding knowledge of the genetic mutations underlying BTCs and represent a promising treatment strategy in molecularly selected subgroups of patients. In addition, the advent of immunotherapy over recent years has dramatically changed the bleak outcomes observed in malignancies such as melanoma. Our growing understanding of the complex tumor microenvironment in BTC has identified mechanisms of tumor immune evasion that could potentially be targeted with immunotherapy. As a result, different immunotherapeutic approaches including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, have been investigated. The use of immunotherapeutic agents is currently only approved for a small subset of treatment-refractory BTCs based on microsatellite instability (MSI) status and tumor mutational burden (TMB), but this will likely change with the potential approval of immunotherapy plus chemotherapy as a result of the TOPAZ-1 trial. MDPI 2022-03-29 /pmc/articles/PMC8996885/ /pubmed/35406520 http://dx.doi.org/10.3390/cancers14071748 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kang, Sandra
El-Rayes, Bassel F.
Akce, Mehmet
Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
title Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
title_full Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
title_fullStr Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
title_full_unstemmed Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
title_short Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
title_sort evolving role of immunotherapy in advanced biliary tract cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996885/
https://www.ncbi.nlm.nih.gov/pubmed/35406520
http://dx.doi.org/10.3390/cancers14071748
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