Dual inhibition of PI3K and mTOR signaling pathways decreases human pancreatic neuroendocrine tumor metastatic progression

Pancreas

Volumn 43, Issue 1, 2014, Pages 88-92

  Djukom, Clarisse ^a   Porro, Laura J ^a   Mrazek, Amy ^a   Townsend, Courtney M ^a   Hellmich, Mark R ^a   Chao, Celia ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

Author keywords

BON cell; liver metastasis; pancreatic neuroendocrine tumor; RAD001

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER GROWTH; CANCER SURVIVAL; CELL GROWTH; CELL GROWTH ASSAY; CELL PROLIFERATION; COMPARATIVE STUDY; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; INTRACELLULAR SIGNALING; LIVER METASTASIS; MOUSE; NONHUMAN; PANCREATIC NEUROENDOCRINE TUMOR; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; TUMOR CELL; WESTERN BLOTTING;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELL PROLIFERATION; CHROMONES; DISEASE PROGRESSION; ENZYME INHIBITORS; FEMALE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LIVER NEOPLASMS; MICE; MICE, NUDE; MORPHOLINES; NEUROENDOCRINE TUMORS; PANCREATIC NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84891560207     PISSN: 08853177     EISSN: 15364828     Source Type: Journal    
DOI: 10.1097/MPA.0b013e3182a44ab4     Document Type: Article

References (18)

1. Yao JC, Hassan M, Phan A, et al. One hundred years after ''carcinoid'': epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26: 3063-3072.
2. Zhou J, Enewold L, Stojadinovic A, et al. Incidence rates of exocrine and endocrine pancreatic cancers in the United States. Cancer Causes Control. 2010;21:853-861.
3. Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135:1469-1492.
4. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514-523.
5. Evers BM, Ishizuka J, Townsend CM Jr., et al. The human carcinoid cell line, BON. A model system for the study of carcinoid tumors. Ann N Y Acad Sci. 1994;733:393-406.
6. von Wichert G, Jehle PM, Hoeflich A, et al. Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res. 2000;60:4573-4581. (Pubitemid 32103642)
7. O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66:1500-1508. (Pubitemid 43259931)
8. Mavrommati I, Maffucci T. mTOR inhibitors: facing new challenges ahead. Curr Med Chem. 2011;18:2743-2762.
9. Jackson LN, Chen LA, Larson SD, et al. Development and characterization of a novel in vivo model of carcinoid syndrome. Clin Cancer Res. 2009;15:2747-2755.
10. Shah T, Hochhauser D, Frow R, et al. Epidermal growth factor receptor expression and activation in neuroendocrine tumours. J Neuroendocrinol. 2006;18:355-360.
11. Zitzmann K, De Toni EN, Brand S, et al. The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology. 2007;85:54-60. (Pubitemid 46550026)
12. Touzios JG, Kiely JM, Pitt SC, et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg. 2005;241:776-785. (Pubitemid 40604923)
13. Tabernero J, Rojo F, Calvo E, et al. Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol. 2008;26:1603-1610.
14. Pitt SC, Chen H, Kunnimalaiyaan M. Inhibition of phosphatidylinositol 3-kinase/Akt signaling suppresses tumor cell proliferation and neuroendocrine marker expression in GI carcinoid tumors. Ann Surg Oncol. 2009;16:2936-2942.
15. Roberts PJ, Usary JE, Darr DB, et al. Combined PI3K/mTOR and MEK inhibition provides broad antitumor activity in faithful murine cancer models. Clin Cancer Res. 2012;18:5290-5303.
16. Maira SM, Stauffer F, Brueggen J, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008;7:1851-1863.
17. Baumann P, Mandl-Weber S, Oduncu F, et al. The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma. Exp Cell Res. 2009;315:485-497.
18. Zitzmann K, von Ruden J, Brand S, et al. Compensatory activation of Akt in response to mTOR and Raf inhibitorsVa rationale for dual-targeted therapy approaches in neuroendocrine tumor disease. Cancer Lett. 2010;295:100-109.