Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors can be functional, i.e., hormone secreting tumors, e.g., insulinoma, gastrinoma or VIPoma, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNET's, usually present later either incidentally or due to tumor bulk symptoms. The recent WHO classification system in 2010 classified PNET's into different stages and grades depending on the mitotic activity and Ki-67 labeling index. PNET's have a broad range of prognoses depending on the histologic grade, differentiation and biologic behavior. Computerized tomographic scanning (CT), magnetic resonance imaging (MRI) and octreoscan are imaging tools used to diagnose PNET, in addition to a confirmatory tissue diagnosis with immunohistochemical stains, typically obtained by either cytologic or histologic assessment. Symptomatic advanced PNET's can be treated with a long-acting somatostatin analogue for those tumors with somatostatin receptor positivity and which may also have antiproliferative activity. Another treatment modality is peptide receptor radionucleotide therapy (PRRT) in somatostatin receptor-positive tumors, albeit as yet with limited availability in the United States. Systemic therapies with combination cytotoxic agents e.g., streptozocin, anthracyclines, and capecitabine and temozolomide, all have established activity in PNET's. Biologic agents targeting the VEGF and mTOR signaling pathways, e.g., sunitinib, bevacizumab or everolimus are becoming integrated as treatments for PNET's. Poorly differentiated, high grade PNETs with a very high mitotic rate are treated with platinum-based chemotherapy regimens similar to treatment paradigms for small cell carcinoma of the lung. For liver confined or predominant disease, strategies such as cytoreductive surgery, hepatic artery embolization or radioembolization are treatment modalities to effect locoregional tumor control. The next generation of studies in PNET will help define optimal sequencing strategies of available therapies and also will attempt to use biomarker-guided approaches to select therapies.
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PMID:Emerging therapies for pancreas neuroendocrine cancers. 2584 79

Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Somatostatin have a broad range of biological actions that include inhibition of exocrine and endocrine secretions, gut motility, cell proliferation, cell survival and angiogenesis. Five somatostatin receptors (SSTR1-SSTR5) have been cloned and characterized. Somatostatin analogues include octreotide and lanreotide are effective medical tools in the treatment and present selectivity for SSTR2 and SSTR5. During treatment is seen disapperance of flushing, normalization of bowel movements and reduction of serotonin and 5-hydroxyindole acetic acid (5-HIAA) secretion. Telotristat represents a novel approach by specifically inhibiting serotonin synthesis and as such, is a promising potential new treatment for patients with carcinoid syndrome. To pancreatic functionig neuroendocrine tumors belongs insulinoma, gastrinoma, glucagonoma and VIP-oma. Medical management in patients with insulinoma include diazoxide which suppresses insulin release. Also mTOR inhibitors may inhibit insulin secretion. Treatment of gastrinoma include both proton pump inhibitors (PPIs) and histamine H2 - receptor antagonists. In patients with glucagonomas hyperglycaemia can be controlled using insulin and oral blood glucose lowering drugs. In malignant glucagonomas smatostatin analogues are effective in controlling necrolytic migratory erythemia. Severe cases of the VIP-oma syndrome require supplementation of fluid losses. Octreotide reduce tumoral VIP secretion and control secretory diarrhoea.
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PMID:Management of the hormonal syndrome of neuroendocrine tumors. 2850 64