Gastroenteropancreatic neuroendocrine neoplasms: epidemiology, genetics, and treatment

Abstract

The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) is increasing at a rapid pace and is becoming an increasingly important consideration in clinical care. Epidemiological data from multiple countries indicate that the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) exhibits regional, site-specific, and gender-based variations. While the genetics and pathogenesis of some GEP NEN, particularly pancreatic NENs, have been investigated, there are still many mechanisms that require further investigation. The management of GEP NEN is diverse, but surgery remains the primary option for most cases. Peptide receptor radionuclide therapy (PRRT) is an effective treatment, and several clinical trials are exploring the potential of immunotherapy and targeted therapy, as well as combination therapy.

Keywords: epidemiology; gastroenteropancreatic neuroendocrine neoplasm; genetics; neuroendocrine tumor; treatment.

Figure 1

The age-adjusted incidence of GEP NEN in the world map.

Figure 2

The mTOR signaling pathway. mTORC1 is linked to 3 input signals, whereas mTORC2 is controlled by a growth factor. AMPK, AMP-activated kinase; ERK, extra-cellular regulated kinase; deptor, DEP-domain-containing mTOR interacting protein; mLST8, mammalian lethal with Sec13 protein 8; mTORC, mammalian target of rapamycin complex; PDK1, phosphoinositide-dependent kinase 1; PI3K, phosphatidylinositol 3-kinase; PIP2, phosphatidylinositol bisphosphate; PIP3, phosphatidylinositol triphosphate; PRAS40, proline-rich Akt1 substrate 1; Rheb, Ras homolog enriched in brain; mSin1, stress activated protein kinase interaction protein 1; protor, protein observed with Rictor-1/; TSC1/2, tuberous sclerosis complex1/2.

Figure 3

The VEGF signaling pathway. The Vascular endothelial growth factor (VEGF) family has 6 ligands (VEGF-A, B, C, D, E, placenta growth factor [PlGF]) that bind specifically to the VEGF receptor to activate different signaling pathways. The phospholipase C isoform-γ (PLCγ)–protein kinase C (PKC) pathway activates Raf protein kinase, and then the downstream Mitogen- activated protein kinase kinases 1 and 2 (MEK1/2), extra-cellular regulated kinase 1/2 (ERK1/2), will be activated sequentially, which can eventually control proliferation. Phosphoinositide 3-kinase (PI3K)/AKT signaling pathway regulates cell survival. In addition, adhesion is associated with focal adhesion kinase (FAK).