Signalling Pathways in Bronchial Neuroendocrine Tumor Disease and Its Translation to Innovative Targets: The New Kid on the Block Abstract #1003

Introduction: Bronchial neuroendocrine neoplasias comprise a wide spectrum of well-differentiated tumors (typical/atypical carcinoids) to undifferentiated carcinomas such as small (SCLC) and large cell (LC) neuroendocrine carcinomas with a fatal prognosis. Therapeutic options are unsatisfactory.
Aim(s): To further elucidate the signalling pathways and crosstalks in order to define potential druggable targets in different neuroendocrine tumor cell lines of the lung. In addition, we define the role of FoxM1 and survivin in the subset of SCLC.
Materials and methods: A wide panel of neuroendocrine tumor cell lines, namely NCI-H727 (typical carcinoid), NCI-H720 (atypical carcinoid), NCI-H810 (LC lung carcinoma), NCI-H2171 (SCLC) and A549 (NSCLC; control) are characterized by FACS analysis and western blot analysis for typical neuroendocrine features. Furthermore, western blot analysis is performed to find differences in crucial signalling axes (PI3K-mTOR; MDM2-p53-pRb; MAPK). One-hundred and forty patients with SCLC (257 specimens) from a single institution (Zentralklinik Bad Berka GmbH) are stained immunohistochemically for FoxM1 and survivin expression.
Conference: 11th Annual ENETS Conference (2014)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: PD Dr. Patricia Grabowski

To read results and conclusion, please login ...

Further abstracts you may be interested in

#344 Cell Cycle Phase Expression Profile Guided Selection of Proliferative Markers for Well-differentiated Small Intestinal Neuroendocrine Neoplasms
Introduction: Grading of neuroendocrine lesions is often determined by Ki-67 (immunostain), despite limited prognostic ability for this cell cycle marker in well-differentiated tumors (WDNETs) and carcinomas.
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: Dr Mark Kidd
Authors: Lawrence B, Kidd M, Alaimo D, Svejda B, ...
#1001 Forkheadbox Proteins as Novel Drug Targets in Gastroenteropancreatic Neuroendocrine Tumor Disease: Inhibition of FoxM1 Exerts Antiproliferative Effects in GEP-NEN Cell Lines
Introduction: Forkheadbox proteins (Fox proteins) are transcriptions factors. They are highly conserved key players in a large number of cellular processes. Fox proteins have been described as acting as both tumor suppressors and oncogenes. Most notably, they operate in the context of the majority of cancer-related pathways. Information about the fuunction of these proteins in gastroenteropancreatic neuroendocrine neoplasias is scant.
Conference: 11th Annual ENETS Conference (2014)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: PD Dr. Patricia Grabowski
#1172 Dual Inhibition of PI3K and mTORC1/C2 by PKI-587 (PF-05212384) as a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease and Its Effect on AKT-Signaling
Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are heterogeneous in their clinical behavior and therapeutic options are still not satisfactory. The “crosstalk” of different signaling pathways in NEN cells appears to be more complex as known already. PKI-587 is a highly potent novel dual inhibitor of PI3K and mTORC1/C2.
Conference: 12th Annual ENETS Conference (2015)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: Helma Freitag
#1301 Role of TSC22D1 (TGFβ-Stimulated Clone 22 Domain Family Member 1) in Bronchial Carcinoids
Introduction: Neuroendocrine tumors (NETs) include bronchial carcinoids, either typical (TC) or atypical (AC). Tsc22d1 encodes for a member of TSC22 domain family of leucine zipper transcription factors; the protein (TSC22D1) is stimulated by TGFβ. Microarray data analysis obtained comparing a pool of TC tissue specimens with a pool of AC tissue specimens shows TSC22D1 down-regulation in AC samples. These data were confirmed by real time PCR and Western blot in vitro models of TC (NCI-H727 cells) and AC (NCI-H720 cells)
Conference: 13th Annual ENETS conference (2016)
Category: Biomarkers
Presenting Author: PhD student Simona Falletta
#1542 Selective Inhibition of PI3Kalpha (BYL719) - Promising Therapeutic Option for Neuroendocrine Tumors?
Introduction: Neuroendocrine tumors are heterogeneous, often functional malignancies and their therapeutic options are limited. As the PI3 kinase signaling is ­in GEP-NENs, selective PI3Kalpha inhibitors may be more potent than panPI3K inhibitors.
Conference: 13th Annual ENETS conference (2016)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: PD Dr. Patricia Grabowski