Somatostatin analogs — from new molecules to new applications

Somatostatin (SST) was firstly discovered as a hypothalamic hormone inhibiting GH secretion. Despite its broad inhibitory effects on both endocrine and exocrine secretions, natural SST has limited therapeutic potential owing to its short plasma half-life. The synthesis of the first two metabolically stabilized and more potent SST analogs (octreotide and lanreotide) established the use of SST peptide therapy. The discovery of the five SST receptor (sst1–5) subtypes in the 1990s further enhanced our understanding of the biological roles of SST, created new therapeutic opportunities and highlighted the limitation of ‘classical’ SST analogs, which act mainly via receptor subtype 2 and are unable to reproduce all actions of native SST. To diminish these limitations, new SST analogs highly selective for particular receptor subtypes, together with so-called ‘universal’ analogs acting on multiple receptor subtypes, have been developed. These compounds have shown promise in preclinical studies and might further advance the use of SST analog therapy in the future. The development of SST analogs coupled to radioisotopes or cytotoxic drugs, which allows the selective destruction of tumor cells overexpressing sst receptors, constitutes another field of progress. [Copyright &y& Elsevier]