The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors

Abstract

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.

Dehydrocostus lactone inhibits in vitro gastrinoma cancer cell growth through apoptosis induction, sub-G1 cell cycle arrest, DNA damage and loss of mitochondrial membrane potential

“…Moreover, treatment options for gastrinoma are limited and are often associated with numerous side effects [1]. The findings of this study indicate that dehydrocostus lactone is a potent cytotoxic agent which induces significant growth inhibitory effects in human pancreatic neuroendocrine tumor cell lines (BON-1) in a time-dependent as well as dose-dependent manner.…”

“…Gastrinomas are also known as pancreatic neuroendocrine tumors. Pancreatic neuroendocrine tumors (PNETs) are malignant tumors likely arising from islet cells of the pancreas [1,2]. Pancreatic neuroendocrine tumors secrete a range of hormones including insulin, glucagon and somatostatin.…”

Neuroendocrine tumor disease: an evolving landscape

“…1). Given the overall indolence of the disease, the prevalence renders GEP-NENs the second most common GI cancer after colon cancer (Schimmack et al 2011), and more prevalent than pancreatic, gastric, esophageal, or hepatic cancer or any two of these combined.…”

“…Tumors release a variety of bioactive products (amines/peptides) that may result in a systemic (carcinoid) syndrome. However, at least 50% of GEP-NENs (w50% of pancreatic and 15-20% of small intestinal (SI)), may be asymptomatic and are characterized as 'nonfunctional' (Schimmack et al 2011). Local (peritoneal w50%) or distant (cardiac w25%) fibrosis may be an issue in EC cell small bowel-derived lesions.…”

Compound gastroenteropancreatic neuroendocrine and gastrointestinal stromal tumors in the stomach: A case report

“…GEP-NETs usually and equally distribute in the foregut (stomach or duodenal), midgut (jejunal, ileal, appendix or proximal colon) and hindgut (distal colon or rectum) (14). Although they are rare neoplastic diseases in general, the incidence has greatly increased in the last decade (15).…”