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Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm

Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas that originate from the epithelial lining of the biliary tree. BTCs are characterized by presentation with advanced disease precluding curative surgery, rising global incidence, and a poor prognosis. Chemotherapy is the mainst...

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Autores principales: Chakrabarti, Sakti, Kamgar, Mandana, Mahipal, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465131/
https://www.ncbi.nlm.nih.gov/pubmed/32722188
http://dx.doi.org/10.3390/cancers12082039
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author Chakrabarti, Sakti
Kamgar, Mandana
Mahipal, Amit
author_facet Chakrabarti, Sakti
Kamgar, Mandana
Mahipal, Amit
author_sort Chakrabarti, Sakti
collection PubMed
description Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas that originate from the epithelial lining of the biliary tree. BTCs are characterized by presentation with advanced disease precluding curative surgery, rising global incidence, and a poor prognosis. Chemotherapy is the mainstay of the current treatment, which results in a median overall survival of less than one year, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous actionable targets, leading to the discovery of new therapies tailored to the molecular targets. Therapies targeting fibroblast growth factor receptor (FGFR) fusion, isocitrate dehydrogenase (IDH) mutations, the human epidermal growth factor receptor (HER) family, DNA damage repair (DDR) pathways, and BRAF mutations have produced early encouraging results in selected patients. Current clinical trials evaluating targeted therapies, as monotherapies and in combination with other agents, are paving the way for novel treatment options. Genomic profiling of cell-free circulating tumor DNA that can assist in the identification of an actionable target is another exciting area of development. In this review, we provide a contemporaneous appraisal of the evolving targeted therapies and the ongoing clinical trials that will likely transform the therapeutic paradigm of BTC.
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spelling pubmed-74651312020-09-04 Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm Chakrabarti, Sakti Kamgar, Mandana Mahipal, Amit Cancers (Basel) Review Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas that originate from the epithelial lining of the biliary tree. BTCs are characterized by presentation with advanced disease precluding curative surgery, rising global incidence, and a poor prognosis. Chemotherapy is the mainstay of the current treatment, which results in a median overall survival of less than one year, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous actionable targets, leading to the discovery of new therapies tailored to the molecular targets. Therapies targeting fibroblast growth factor receptor (FGFR) fusion, isocitrate dehydrogenase (IDH) mutations, the human epidermal growth factor receptor (HER) family, DNA damage repair (DDR) pathways, and BRAF mutations have produced early encouraging results in selected patients. Current clinical trials evaluating targeted therapies, as monotherapies and in combination with other agents, are paving the way for novel treatment options. Genomic profiling of cell-free circulating tumor DNA that can assist in the identification of an actionable target is another exciting area of development. In this review, we provide a contemporaneous appraisal of the evolving targeted therapies and the ongoing clinical trials that will likely transform the therapeutic paradigm of BTC. MDPI 2020-07-24 /pmc/articles/PMC7465131/ /pubmed/32722188 http://dx.doi.org/10.3390/cancers12082039 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chakrabarti, Sakti
Kamgar, Mandana
Mahipal, Amit
Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm
title Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm
title_full Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm
title_fullStr Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm
title_full_unstemmed Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm
title_short Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm
title_sort targeted therapies in advanced biliary tract cancer: an evolving paradigm
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465131/
https://www.ncbi.nlm.nih.gov/pubmed/32722188
http://dx.doi.org/10.3390/cancers12082039
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