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Growth factor-receptor pathway interfering treatment by somatostatin analogs and suramin: preclinical and clinical
J G Klijn1, B Setyono-Han, G H Bakker
1Division of Endocrine Oncology, (Department of Medical Oncology), Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Unlabelled:
Interference in growth factor mediated pathways is a new strategy in the treatment of cancer. Somatostatin analogs can inhibit hormone and growth factor secretion, while suramin can block the binding of several growth factors to their receptors. In addition, somatostatin analogs can cause direct growth inhibitory effects after binding to tumoral somatostatin receptors. We tested the efficacy and endocrine effects of chronic treatment with three somatostatin analogs (Sandostatin, R RC-160 and CGP 15-425) or suramin in several tumor models and in patients with various types of cancer. Treatment with somatostatin analogs caused growth inhibition of breast cancer cells (MCF-7) in vitro, and of rat transplantable pancreatic (50-70% inhibition) and prostatic Dunning tumors (12% inhibition). No tumor growth inhibition was observed with respect to DMBA-induced rat mammary tumors, a transplantable colon tumor and a rhabdomyosarcoma in rats. In 34 patients with metastatic pancreatic or gastrointestinal adenocarcinomas chronic Sandostatin treatment caused stable disease in 27% of the patients, but no objective remissions. Somatostatin receptors were found in the responding MCF-7 mammary tumor cells, rat pancreatic tumors and in 20-45% of human breast cancer specimens [J. Steroid Biochem. Molec. Biol. 37 (1990) 1073-1077], but not in rat DMBA-mammary tumors or in 10 human pancreatic adenocarcinomas. Suramin caused significant dose-dependent growth inhibition of human breast cancer cells in vitro and of rat pancreatic tumors in vivo in the presence of plasma levels up to 150 micrograms/ml. In a preliminary clinical study concerning 11 patients with various tumor types we observed significant hematological, biochemical, endocrine and clinical side effects, but no objective remissions in spite of relevant peak plasma suramin concentrations of 270-330 micrograms/ml.
In Conclusion:
somatostatin analogs and suramin can cause growth inhibition of various experimental tumors in vitro and in vivo, but the clinical value has to be established for several types of cancer, especially with respect to suramin and suramin-like compounds.
Insights
Somatostatin analogs and suramin show promise in inhibiting experimental tumor growth. Further clinical studies are needed to establish their value in treating various cancers, particularly suramin-based therapies.
Area of Science:
- Oncology
- Pharmacology
Background:
- Interference with growth factor pathways is a novel cancer treatment strategy.
- Somatostatin analogs inhibit growth factor secretion and act directly on tumoral somatostatin receptors.
- Suramin blocks growth factor binding to their receptors.
Purpose of the Study:
- To evaluate the efficacy and endocrine effects of somatostatin analogs and suramin in preclinical tumor models and human cancer patients.
- To investigate the presence of somatostatin receptors in various tumor types.
Main Methods:
- Treatment with somatostatin analogs (Sandostatin, R RC-160, CGP 15-425) or suramin in vitro and in vivo tumor models.
- Assessment of tumor growth inhibition and endocrine effects in 34 patients with metastatic pancreatic or gastrointestinal adenocarcinomas.
- Analysis of somatostatin receptor expression in tumor samples.
Main Results:
- Somatostatin analogs inhibited MCF-7 breast cancer cells, rat pancreatic, and prostatic tumors.
- No significant inhibition was observed for DMBA-induced mammary tumors, colon tumors, or rhabdomyosarcomas.
- Sandostatin treatment in patients resulted in stable disease for 27% but no objective remissions.
- Suramin demonstrated dose-dependent growth inhibition of breast cancer cells and rat pancreatic tumors.
- Suramin treatment in patients caused significant side effects with no objective remissions.
Conclusions:
- Somatostatin analogs and suramin exhibit growth inhibitory effects on experimental tumors.
- The clinical utility of these agents requires further investigation, especially for suramin and related compounds in specific cancer types.