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Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors.

TitleMassive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors.
Publication TypeJournal Article
Year of Publication2016
AuthorsWalter, R. Fred Henry, Vollbrecht C., Christoph D., Werner R., Schmeller J., Flom E., Trakada G., Rapti A., Adamidis V., Hohenforst-Schmidt W., Kollmeier J., Mairinger T., Wohlschlaeger J., Zarogoulidis P., Porpodis K., Schmidt K. Werner, & Mairinger F. Dominik
JournalJ Cancer
Volume7
Issue15
Pagination2165-2172
Date Published2016
ISSN1837-9664
Abstract

: 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. : 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. : 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, expression was observed in the investigated tumors in a noteworthy manner. Additionally, was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, , was nearly absent in all low-grade tumors. showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. : Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors.

DOI10.7150/jca.16925
Alternate JournalJ Cancer
PubMed ID27994651
PubMed Central IDPMC5166524

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