Rationale for the use of somatostatin analogs as antitumor agents

Susini, Christiane; Buscail, Louis

doi:10.1093/annonc/mdl105

Cited by 265 publications

(218 citation statements)

References 93 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…As octreotide is also known to have indirect effects, such as central effects on GH release and proposed effects on angiogenesis (Susini & Buscail 2006) that may modulate in vivo growth, we next evaluated the effect of octreotide and rapamycin, alone and in combination, in mice bearing BON xenografts. BON cells were injected into the upper right flanks of male BALB/c mice, and 8 days after inoculation, mice were divided into six groups and treated with long-acting octreotide (Sandostatin LAR) alone (30 mg/kg), octreotide vehicle, rapamycin alone (15 mg/kg), rapamycin vehicle DMSO, rapamycin and octreotide, and combination vehicle.…”

Section: Rapamycin and Octreotide Antitumor Activity In Vivomentioning

confidence: 99%

Antitumor activity of rapamycin and octreotide as single agents or in combination in neuroendocrine tumors

Moreno¹,

Akçakanat

Munsell³

et al. 2008

Endocrine Related Cancer

136

View full text Add to dashboard Cite

The mammalian target of rapamycin (mTOR) signaling pathway has emerged as a promising target for cancer therapy. Rapamycin inhibits mTOR activity but induces upstream signaling, leading to Akt activation, potentially limiting antitumor activity. Octreotide, a somatostatin analog, decreases phosphatidylinositol-3-kinase/Akt signaling in some models, and thus theoretically may enhance rapamycin's antitumor activity. The aim of this study was to determine the antitumor activity of rapamycin and octreotide as single agents and in combination in neuroendocrine tumors. In carcinoid cell lines BON-1 and NCI-H727, cell proliferation was significantly inhibited by rapamycin in vitro, although rapamycin treatment did lead to Akt phosphorylation. Octreotide had limited antiproliferative effects alone, and did not demonstrate synergistic or additive interactions with rapamycin. Furthermore, octreotide did not overcome rapamycin-induced Akt phosphorylation. In vivo, rapamycin alone caused significant tumor suppression. Octreotide alone did not inhibit in vivo tumor growth and did not enhance rapamycin-mediated growth inhibition. In conclusion, rapamycin causes significant growth inhibition in carcinoid tumor cell lines in vitro and in vivo, thus mTOR is a promising therapeutic target for neuroendocrine tumors. Octreotide does not enhance the efficacy of rapamycin's antiproliferative effects in the models tested, and does not inhibit rapamycin-mediated feedback activation of Akt. Further study is needed in order to determine whether octreotide or other somatostatin analogs enhance the efficacy of mTOR inhibitors in other models.

show abstract

Section: Rapamycin and Octreotide Antitumor Activity In Vivomentioning

confidence: 99%

Antitumor activity of rapamycin and octreotide as single agents or in combination in neuroendocrine tumors

Moreno¹,

Akçakanat

Munsell³

et al. 2008

Endocrine Related Cancer

136

View full text Add to dashboard Cite

show abstract

“…Even before its approval, case reports suggested that octreotide showed antitumor properties for patients with NETs [18,19]. Reviews of preclinical studies suggest direct receptor-mediated antitumor effects of cell cycle inhibition, growth factor inhibition, and proapoptotic activity [20,21]. Furthermore, there may be indirect effects, including inhibition of the release of growth factor and trophic hormones, inhibition of angiogenesis, and modulation of the immune system [20,21].…”

Section: Introductionmentioning

confidence: 99%

Antitumor Effects of Somatostatin Analogs in Neuroendocrine Tumors

2012

View full text Add to dashboard Cite

Background. For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs.Methods. A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts.Results. In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease

show abstract

“…Furthermore, consistently with the model of glucocorticoid-mediated down-regulation of sstr2, pretreatment of AtT20 cells with dexamethasone abolished the inhibitory effects of octreotide on ACTH secretion, but had no effect on the inhibitory action of pasireotide or somatostatin-14 [70]. Somatostatin analogues may also confer an indirect anti-proliferative effect through inhibition of angiogenesis (down-regulation of vascular endothelial growth factor), which limits tumour growth [74], and by reducing levels of growth factors and trophic hormones [74].…”

Section: Emerging Drugs For Cushing's Diseasementioning

confidence: 88%