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Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors
Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased surviva...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166524/ https://www.ncbi.nlm.nih.gov/pubmed/27994651 http://dx.doi.org/10.7150/jca.16925 |
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author | Walter, Robert Fred Henry Vollbrecht, Claudia Christoph, Daniel Werner, Robert Schmeller, Jan Flom, Elena Trakada, Georgia Rapti, Aggeliki Adamidis, Vasilis Hohenforst-Schmidt, Wolfgang Kollmeier, Jens Mairinger, Thomas Wohlschlaeger, Jeremias Zarogoulidis, Paul Porpodis, Konstantinos Schmidt, Kurt Werner Mairinger, Fabian Dominik |
author_facet | Walter, Robert Fred Henry Vollbrecht, Claudia Christoph, Daniel Werner, Robert Schmeller, Jan Flom, Elena Trakada, Georgia Rapti, Aggeliki Adamidis, Vasilis Hohenforst-Schmidt, Wolfgang Kollmeier, Jens Mairinger, Thomas Wohlschlaeger, Jeremias Zarogoulidis, Paul Porpodis, Konstantinos Schmidt, Kurt Werner Mairinger, Fabian Dominik |
author_sort | Walter, Robert Fred Henry |
collection | PubMed |
description | Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors. |
format | Online Article Text |
id | pubmed-5166524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-51665242016-12-19 Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors Walter, Robert Fred Henry Vollbrecht, Claudia Christoph, Daniel Werner, Robert Schmeller, Jan Flom, Elena Trakada, Georgia Rapti, Aggeliki Adamidis, Vasilis Hohenforst-Schmidt, Wolfgang Kollmeier, Jens Mairinger, Thomas Wohlschlaeger, Jeremias Zarogoulidis, Paul Porpodis, Konstantinos Schmidt, Kurt Werner Mairinger, Fabian Dominik J Cancer Research Paper Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors. Ivyspring International Publisher 2016-10-25 /pmc/articles/PMC5166524/ /pubmed/27994651 http://dx.doi.org/10.7150/jca.16925 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. |
spellingShingle | Research Paper Walter, Robert Fred Henry Vollbrecht, Claudia Christoph, Daniel Werner, Robert Schmeller, Jan Flom, Elena Trakada, Georgia Rapti, Aggeliki Adamidis, Vasilis Hohenforst-Schmidt, Wolfgang Kollmeier, Jens Mairinger, Thomas Wohlschlaeger, Jeremias Zarogoulidis, Paul Porpodis, Konstantinos Schmidt, Kurt Werner Mairinger, Fabian Dominik Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors |
title | Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors |
title_full | Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors |
title_fullStr | Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors |
title_full_unstemmed | Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors |
title_short | Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors |
title_sort | massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166524/ https://www.ncbi.nlm.nih.gov/pubmed/27994651 http://dx.doi.org/10.7150/jca.16925 |
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