Antitumor activity of Pasireotide (SOM230) alone and in combination with Everolimus (RAD001) in DU-145 human prostate cancer model Abstract #19

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)
Category: Basic
Presenting Author: Dr. Herbert A. Schmid

To read results and conclusion, please login ...

Further abstracts you may be interested in

#131 Efficacy and safety results from a Phase II study of pasireotide (SOM230) in the treatment of patients with metastatic NETs refractory or resistant to octreotide LAR
Introduction: Pasireotide, a multi-receptor targeted somatostatin analogue, has 30-, 5- and 39-fold greater affinity for sst1,3 and sst5 receptors, respectively, and a slightly lower affinity for sst2, than octreotide. Because of this multi-receptor binding profile, pasireotide may be effective in controlling symptoms of carcinoid syndrome in patients with gastroenteropancreatic neuroendocrine tumors (NETs) who are no longer responsive to currently available somatostatin analogues.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr Larry K Kvols
#151 Rationale for combining mTOR with other targeted agents in the treatment of neuroendocrine tumors
Introduction: Advanced neuroendocrine tumors (NETs) are aggressive and incurable with standard treatment. Many cellular targets are being evaluated in this patient population, including mammalian target of rapamycin (mTOR), a kinase that is the central regulator of several signaling pathways related to cell growth, angiogenesis, and bioenergetics. Because mTOR serves as a neoplastic switch activated by many cancer-related mutations, mTOR inhibition may have broad efficacy across tumor types, including NETs. Somatostatin analogs (SSAs) have long been used to treat carcinoid symptoms in NET patients. The SSA octreotide long-acting release (LAR) demonstrated significant antitumor effects against advanced midgut NETs in the phase III PROMID study.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Kjell Öberg
Authors: Öberg K, Yao J C, ...
#302 Monoclonal Antibodies Against the Human Somatostatin Receptor Subtypes 1-5: Characterization and Immunohistochemical Application in Gastrointestinal Neuroendocrine Tumors
Introduction: A lack of well-characterized somatostatin receptor (sstr)-specific antibodies has hampered development of routine sstr expression profiles that may be useful in the treatment of NET patients (pts).
Conference: 8th Annual ENETS Conference (2011)
Category: Clinical
Presenting Author: Chiara Lambertini
#350 RAD001 and Octreotide LAR as first-line treatment of well differentiated neuroendocrine tumors: an I.T.M.O. (Italian Trials in Medical Oncology) group study
Introduction: RAD001 has shown antitumor activity in pancreatic neuroendocrine tumors (NETs) and it seems to work synergistically with somatostatine analogues.

Conference:
Category: Basic
Presenting Author: Dr Laura Catena
#447 SOMscan: Towards a Ga-68-labeled Pan-Somatostatin PET Imaging Probe Based on SOM230 (Pasireotide)
Introduction: The somatostatin receptor subtype sst2 is largely expressed on neuroendocrine tumors. However, current clinical studies indicate that the subtypes sst1, 3, 5 are of substantial relevance as well.
Conference: 9th Annual ENETS Conference (2012)
Category: Basic
Presenting Author: Dr. Melpomeni Fani
Authors: Fani M, Braun F, Mann A, Kiewer A, ...
Keywords: SOM230, Ga-68, PET imaging
Close
Notice
Important Notice:

In preparation of the upcoming ENETS Barcelona 2018 Annual Conference, we have discovered in the world wide web at least one professional entity suggestive of possessing an ENETS mandate for conference registrations. Therefore, we must inform you that 100% of all conference participants are registered through ENETS official website www.enets.org and http://enetsconference.org/. There are no further options to validly register for Barcelona 2018 (or for any other ENETS event).

Please stay away from fraudulent scams abusing the ENETS acronym to register – and charge you above official ENETS conference fees! Such entities, against whom ENETS presses criminal charges, are neither authorized, nor commissioned nor instructed by ENETS to make such representations.