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Induction of Apoptosis with Hybrids of Arg-Gly-Asp Molecules and Peptides and Antimitotic Effects of Hybrids of Cytostatic Drugs and Peptides

¹ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
² Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
³ Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands

The presence of a high density of somatostatin receptors (SSRs) on human tumors forms the basis for the successful visualization of primary tumors and their metastases using radiolabeled somatostatin analogs. In recent years somatostatin analogs, coupled to ß-emitting radioisotopes, have been successfully applied in the treatment of patients with metastatic SSR-positive neuroendocrine tumors. This concept of targeting SSR-expressing tumors using peptide receptor radionuclide therapy may also apply to the use of somatostatin analogs coupled to chemotherapeutic compounds. Evidence for the effectiveness of such cytotoxic somatostatin analogs as antitumor agents has been provided in a significant number of studies in experimental tumor models. In addition to cytotoxic somatostatin analogs, somatostatin analogs coupled to peptides containing arginine, glycine, and aspartate and coupled to paclitaxel have been synthesized. Here we discuss the development of the different cytotoxic somatostatin analogs and their antitumor effects in vitro and in vivo in experimental models.

Key Words: somatostatin analogs • somatostatin receptors • apoptosis; cytotoxic agents