More than 30 years have passed since
somatostatin was discovered and its hormonal function defined. The wide range of anatomical distribution and actions of
somatostatin and its receptors have stimulated intense scientific and clinical interest. The development of
somatostatin analogues helped define its usefulness in the treatment of
endocrine diseases and
cancer. The molecular cloning of five distinct subtypes of
somatostatin receptors in the 1980s has significantly increased our insight into the biology of
somatostatin and its receptor subtypes and has led to the design and development of subtype-selective
peptides and nonpeptide agonists and antagonists. In the future, the development of
somatostatin-receptor-mediated treatment will go along different lines.
Tumor-targeted radioactive treatment based on
somatostatin analogues will be further developed and improved. New
somatostatin analogues will come into clinical practice, both receptor subtype-specific analogues, but also pan-receptor analogues. One is currently in clinical trial--SOM230--which is a cyclo-hexapeptide binding with high affinity to receptor type 1, 2, 3 and 5, but not 4. It has already shown activity both in
acromegaly and in neuroendocrine gastrointestinal
tumors. Preclinical studies on
somatostatin analogues, coupled to
cytotoxic agents, have shown rather promising results and will hopefully be further developed in clinical trials. Another interesting area is treatment of neuroendocrine gut
tumors with ultra-high doses of
somatostatin analogues, which has demonstrated significant clinical effects in patients resistant to standard-dose treatment with the same
somatostatin analogue.