title: PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.
abstract: Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due to the lack of a broad mechanistic knowledge, an insufficient classification of specific diagnostic sub-groups, and predictive markers. GEP-NEN tumors evade early diagnosis because of slow asymptomatic growth behavior and are frequently not detected until metastasized. How signaling networks contribute to tumor progression and how these networks interact remains unclear in large parts. In this review we summarize the knowledge on the growth factor responsive non-angiogenetic pathways in sporadic GEP-NENs, highlight promising mechanistic research approaches, and describe important therapy targets.
authors.affiliation: 1. Medizinische Klinik 1 CBF, Dept. of Gastroenterology, Infectious Diseases, Rheumatology CC13, Charité Berlin, Germany; ; 2. Freie Universität Berlin, Institute for Chemistry and Biochemistry, Berlin, Germany;
authors.forename: Franziska
authors.initials: F
authors.lastname: Briest
authors.affiliation: 1. Medizinische Klinik 1 CBF, Dept. of Gastroenterology, Infectious Diseases, Rheumatology CC13, Charité Berlin, Germany; ; 3. Department of Hematology and Internal Oncology and Center for Neuroendocrine Tumours Bad Berka - ENETS Center of Excellence, Zentralklinik Bad Berka, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Grabowski
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D013004:Somatostatin / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1; D013004:Somatostatin; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: Gastroenteropancreatic neuroendocrine neoplasms; biotherapy; growth factors; inhibitor.; kinases; molecular biology; signal transduction