Τίτλος:
Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Henry Walter, R.F.
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.W.
Mairinger, F.D.
Περιοδικό:
EUROPEAN JOURNAL OF CANCER
Εκδότης:
Ivyspring International Publisher
Λέξεις-κλειδιά:
cyclin dependent kinase inhibitor 2A; epidermal growth factor receptor; fibroblast growth factor receptor 1; mammalian target of rapamycin; protein MDM2; scatter factor receptor; somatomedin B; somatomedin C; vasculotropin receptor 2; vasculotropin receptor 3, adult; ALK gene; Article; CDKN2A gene; controlled study; FGFR1 gene; FIGF gene; FLT4 gene; gene expression; gene mutation; gene sequence; human; human tissue; IGF1 gene; IGF2 gene; KDR gene; KIT gene; large cell neuroendocrine carcinoma; lung tumor; MDM2 gene; MET gene; middle aged; mRNA expression assay; MTOR gene; mutation rate; neuroendocrine tumor; next generation sequencing; non small cell lung cancer; NRAS gene; oncogene H ras; PIK3CA gene; small cell lung cancer; therapy resistance; tumor gene
