Introduction: Pasireotide (SOM230) is a novel multi-receptor ligand somatostatin analogue with high affinity for somatostatin receptor subtypes sst1,2,3 and sst5. Like octreotide, which binds primarily to sst2, it inhibits hypersecretion of hormones from patients with functional pituitary tumors and gastroenteropancreatic neuroendocrine (GEP/NET) tumors. In addition, tumor shrinkage has been observed with both compounds in patients with acromegaly, Cushing’s disease and GEP/NETs, but its tumor-reducing mechanism of action has so far not been revealed. In patients with breast and liver cancer, octreotide had little or no antitumor activity.
Aim(s): To investigate the effect of pasireotiede alone and in combination with the mTOR inhibitor Everolimus in a model of humor prostate cancer.
Materials and methods: In prostate tumors, expression of sst1 and sst5 at the membrane and sst4 in the cytosol has been reported, while in a human prostate tumor model (DU-145), sst5 was present at the membrane and sst2 in the cytosol. DU145 human tumor cells were injected s.c. into nude rats and after tumors had established (>100mm3) rats were treated with pasireotide long acting release (LAR) formulation or everolimus alone and in combination. Glucose and IGF-1 levels were determined from blood samples by RIA and pIGF-1R, pIRS1, pS6, pAKT were determined from tumor tissues by immunhistochemically and/or by western blots.
Conference: 7th Annual ENETS Conference (2010)
Presenting Author: Dr. Herbert A. Schmid
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