Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications

Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic im...

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Autores principales:	Hendrien Kuipers, Tessa J. J. de Bitter, Marieke T. de Boer, Rachel S. van der Post, Maarten W. Nijkamp, Philip R. de Reuver, Rudolf S. N. Fehrmann, Frederik J. H. Hoogwater
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	gallbladder cancer gene mutations genetic alterations tumor mutational burden microsatellite instability targeted therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3bcaf37b434c4c129dc68b05009fc95b
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spelling	oai:doaj.org-article:3bcaf37b434c4c129dc68b05009fc95b2021-11-11T15:26:28ZGallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications10.3390/cancers132152572072-6694https://doaj.org/article/3bcaf37b434c4c129dc68b05009fc95b2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5257https://doaj.org/toc/2072-6694Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic implications. A literature search was performed utilizing PubMed, EMBASE, Cochrane Library, and Web of Science. Only studies reporting genetic alterations in human GBC were included. In total, data were extracted from 62 articles, describing a total of 3893 GBC samples. Frequently detected genetic alterations (>5% in >5 samples across all studies) in GBC for which targeted therapies are available in other cancer types included mutations in <i>ATM</i>, <i>ERBB2</i>, and <i>PIK3CA</i>, and <i>ERBB2</i> amplifications. High tumor mutational burden (TMB-H) and microsatellite instability (MSI-H) were infrequently observed in GBC (1.7% and 3.5%, respectively). For solid cancers with TMB-H or MSI-H pembrolizumab is FDA-approved and shows an objective response rates of 50% for TMB-H GBC and 41% for MSI-H biliary tract cancer. Only nine clinical trials evaluated targeted therapies in GBC directed at frequently altered genes (<i>ERBB2</i>, <i>ARID1A</i>, <i>ATM</i>, and <i>KRAS</i>). This underlines the challenges to perform such clinical trials in this rare, heterogeneous cancer type and emphasizes the need for multicenter clinical trials.Hendrien KuipersTessa J. J. de BitterMarieke T. de BoerRachel S. van der PostMaarten W. NijkampPhilip R. de ReuverRudolf S. N. FehrmannFrederik J. H. HoogwaterMDPI AGarticlegallbladder cancergene mutationsgenetic alterationstumor mutational burdenmicrosatellite instabilitytargeted therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5257, p 5257 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gallbladder cancer gene mutations genetic alterations tumor mutational burden microsatellite instability targeted therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	gallbladder cancer gene mutations genetic alterations tumor mutational burden microsatellite instability targeted therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hendrien Kuipers Tessa J. J. de Bitter Marieke T. de Boer Rachel S. van der Post Maarten W. Nijkamp Philip R. de Reuver Rudolf S. N. Fehrmann Frederik J. H. Hoogwater Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications
description	Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic implications. A literature search was performed utilizing PubMed, EMBASE, Cochrane Library, and Web of Science. Only studies reporting genetic alterations in human GBC were included. In total, data were extracted from 62 articles, describing a total of 3893 GBC samples. Frequently detected genetic alterations (>5% in >5 samples across all studies) in GBC for which targeted therapies are available in other cancer types included mutations in <i>ATM</i>, <i>ERBB2</i>, and <i>PIK3CA</i>, and <i>ERBB2</i> amplifications. High tumor mutational burden (TMB-H) and microsatellite instability (MSI-H) were infrequently observed in GBC (1.7% and 3.5%, respectively). For solid cancers with TMB-H or MSI-H pembrolizumab is FDA-approved and shows an objective response rates of 50% for TMB-H GBC and 41% for MSI-H biliary tract cancer. Only nine clinical trials evaluated targeted therapies in GBC directed at frequently altered genes (<i>ERBB2</i>, <i>ARID1A</i>, <i>ATM</i>, and <i>KRAS</i>). This underlines the challenges to perform such clinical trials in this rare, heterogeneous cancer type and emphasizes the need for multicenter clinical trials.
format	article
author	Hendrien Kuipers Tessa J. J. de Bitter Marieke T. de Boer Rachel S. van der Post Maarten W. Nijkamp Philip R. de Reuver Rudolf S. N. Fehrmann Frederik J. H. Hoogwater
author_facet	Hendrien Kuipers Tessa J. J. de Bitter Marieke T. de Boer Rachel S. van der Post Maarten W. Nijkamp Philip R. de Reuver Rudolf S. N. Fehrmann Frederik J. H. Hoogwater
author_sort	Hendrien Kuipers
title	Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications
title_short	Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications
title_full	Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications
title_fullStr	Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications
title_full_unstemmed	Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications
title_sort	gallbladder cancer: current insights in genetic alterations and their possible therapeutic implications
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3bcaf37b434c4c129dc68b05009fc95b
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Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications

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