title: The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors.
abstract: BACKGROUND
  Recent data demonstrate that the incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased exponentially (overall ~500%) over the last three decades, thus refuting the erroneous concept of rarity. GEP-NETs comprise 2% of all malignancies and in terms of prevalence, are the second commonest gastrointestinal malignancy after colorectal cancer. Diagnosis is usually late since there is no biochemical screening test and symptoms are protean and overlooked. As a consequence, 60-80% exhibit metastases with a consequent suboptimal outcome.
  
  
  CONCLUSIONS
  The gastrointestinal tract and pancreas exhibit ~17 different neuroendocrine cell types, but neither the cell of origin nor the biological basis of GEP-NETs is understood. This review examines GEP-NETs from the cellular and molecular perspective and addresses the distinct patterns of functional tumor biology pertinent to clinicians. Although grouped as a neoplastic entity (NETs), each lesion is derived from distinct cell precursors, produces specific bioactive products, exhibits distinct chromosomal abnormalities and somatic mutation events and has uniquely dissimilar clinical presentations. GEP-NETs demonstrate very different survival rates reflecting the intrinsic differences in malignant potential and variations in proliferative regulation. Apart from the identification of the inhibitory role of the somatostatin receptors, there is limited biological knowledge of the key regulators of proliferation and hence a paucity of successful targeted therapeutic agents. IGF-I, TGFβ and a variety of tyrosine kinases have been postulated as key regulatory elements; rigorous data is still required to define predictably effective and rational therapeutic strategy in an individual tumor. A critical issue in the clinical management of GEP-NETs is the need to appreciate both the neuroendocrine commonalities of the disease as well as the unique characteristics of each tumor. The further acquisition of a detailed biological and molecular appreciation of GEP-NETs is vital to the development of effective management strategy.
authors.affiliation: Gastrointestinal Pathobiology Research Group, Department of Gastroenterological Surgery, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Schimmack
authors.forename: Bernhard
authors.initials: B
authors.lastname: Svejda
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lawrence
authors.forename: Mark
authors.initials: M
authors.lastname: Kidd
authors.forename: Irvin M
authors.initials: IM
authors.lastname: Modlin
mesh_terms: D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D006801:Humans; D008297:Male; D018358:Neuroendocrine Tumors / Q000453:epidemiology* / Q000473:pathology* / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D012701:Serotonin / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D012701:Serotonin; D013004:Somatostatin