Growth Hormone Inhibitors in Prostate Cancer: A Systematic Analysis

Abstract

Objective: Despite initial therapeutic success through androgen ablation in patients with advanced prostate cancer, the vast majority progress to androgen independence. Somatostatin (SST) analogs are a viable therapeutic modality before resorting to chemotherapy or immunotherapy. Their mechanism of action is related to a reduction in the IGF-1 (survival factor, reaction on neuroendocrine cells) appearing incrementally after long-term androgen deprivation and a possible suppression of GnRH receptors in prostate cancer following exposure to LHRH agonists. Methods: The computerized databases Medline, NCBI and OMIM were searched for the terms, somatostatin and prostate cancer, in parallel with printed bibliographic references. Forty-two studies were included and 267 patients with androgen-independent prostate cancer (AIPC) who were treated with SST analogs alone or in combination with other medications, e.g. dexamethasone, were analyzed. Results: In 42 studies with 267 AIPC patients, SST analogs were found to be effective, particularly when combined with estrogens or corticosteroids. The side effects are mild and related to the gastrointestinal tract. Conclusions: It would be interesting to study SST analogs in randomized trials including patients with well-defined AIPC. Whether SST analogs could be given earlier during sequential hormonal therapy remains to be studied.

Serotonin and Melatonin Do Not Play a Prominent Role in the Growth of Prostate Cancer Cell Lines

“…Many biologic factors capable of influencing or regulating cell growth have been implicated and probably are involved [24,25] . MLT has been shown to have an influence on cancer cell growth in several cancer entities including PCa cells growing in vitro [26,27] .…”

Mechanisms and Influence of Octreotide-Induced Regulation of Somatostatin Receptor 2 on Hepatocellular Carcinoma

“…Interestingly, studies [5][6][7][8][9][10][11][12][13] have shown that SST can inhibit the growth of many tumors, including neuroendocrine tumors, gastric carcinoma, colonic carcinoma, mastocarcinoma, pancreatic carcinoma, gallbladder carcinoma and HCC. It was suggested that SST might kill tumor cells via its receptors (SSTR1 to SSTR5) which are located on the cell membranes.…”

Visualization of Somatostatin Receptors in Prostate Cancer and its Bone Metastases with Ga-68–DOTATOC PET/CT

“…This is explained by clonal selection of androgen-independent cells present at the initial stage and/or of cells that become androgen independent through mutation within the androgen receptor gene during androgen deprivation. The androgen-independent prostate cancer, though resistant to castration, is still sensitive to secondary hormonal manipulations among which somatostatins are of interest [2,9]. Due to the short plasma half-life of somatostatin (about 2 min), their analogs like octreotide and lanreotide had to be used for therapy.…”

“…The aforementioned therapeutic results were achieved even with somatostatin analogs that primarily address the SSTR2 receptor which is only expressed in fibromuscular (stromal) [13,14] and not in prostate cancer cells. Although the somatostatin receptor subtype addressed by current somatostatin analogs (SSTR2) [15] is responsible for the suppression of GH, better results could be expected if the SSTR1 and SSTR4 receptors are also addressed-which are preferentially expressed in prostate cancer [2,13,16].…”

“…Recently, combination therapies with somatostatin analogs have emerged as a therapeutic option before resorting to chemotherapy or immunotherapy [2]. The therapy with somatostatin analogs requires expression of somatostatin receptors.…”