Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

Abstract

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1%-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC) on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO) classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC), will be needed to improve the prognosis.

Features of chronic pancreatitis by endoscopic ultrasound influence the diagnostic accuracy of endoscopic ultrasound‐guided fine‐needle aspiration of small pancreatic lesions

“…Neuroendocrine tumor tended to occur in few CP patients in the present study, suggesting that NET may not be related to CP. The origin of pancreatic cancer and NET is believed to be different based on their varying genetic backgrounds, 43 and the present findings also showed differences in the CP status in the background pancreatic parenchyma and duct.…”

Gastroenteropancreatic High-Grade Neuroendocrine Neoplasms: Histology and Molecular Analysis, Two Sides of the Same Coin

“…This result was discordant with the protein expression loss of Rb1. Most of the studies looking at Rb1 expression in NECs use immunohistochemistry as a tool, and it has also been proposed to use the Rb1 stain for distinguishing the ambiguous cases of H-NENs [12,35]. The striking difference seen in our data points to the possibility of other molecular events (like methylation) affecting Rb1 protein expression.…”

Novel systemic therapy against malignant pleural mesothelioma

“…Mutations in genes involved in PI3K signaling have been identified in MPM and are thought to contribute to the pathogenesis of MPM (109). Everolimus inhibits PI3K through binding mTOR and is FDA approved for metastatic breast cancer, renal cell carcinoma, subependymal giant cell astrocytoma, GI and lung neuroendocrine tumors, and for prevention of graft failure (110)(111)(112)(113). Unfortunately, patients with MPM who had progressed after first line therapy did not respond to everolimus in a phase II study (114).…”