The Biological and Clinical Relevance of the Somatostatin Receptor
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FOREWORD
The initial discovery of somatostatin was widely hailed as a significant advance in physiology and biology. Few, however, envisaged the impact that this peptide would have on the clinical arena. After a spate of reports documenting its localization, physiological, and pharmacological actions, attention turned to the regulation of intracellular events and the receptors which mediated its effects. Suffice it to say that within a decade a series of long-acting analogs had been synthesized, and focus had been directed to clinical applications. The inhibition of cell secretion, particularly in the gut, led to important considerations in the management of neuroendocrine secretory tumors. Further elaboration of the family of receptor subtypes led to the consideration of differential regulation of not only secretion but also cell growth. The concept of radiosotopically labeling the molecule and using its uptake on tumor receptors provided a unique clinical tool for the localization of neoplasia-expressing somatostatin receptors. The subsequent amplification of this concept to utilize an isotope capable of delivering therapeutic doses of radiation to such lesions has engendered considerable clinical interest and may well have substantial therapeutic benefit. Further developments including the formulation of longer-acting analogs and the recognition that their inhibitory actions may apply not only to secretory events but also to proliferative events has aroused both considerable scientific and clinical interest.
This meeting could not have been held without the generous support of Mallinckrodt Pharmaceuticals and the Yale University School of Medicine. It gathered many experts from numerous countries whose fields ranged from the cellular and molecular domain to the clinical areas of diagnostic and therapeutic strategies. It facilitated consideration of the basic molecular mechanisms of somatostatin and its receptor activation in the context of the clinical applications in diverse disease processes. Of particular interest were the broad discussions relating clinical efficacy not only in terms of symptom management but to tumor diagnosis and therapy. A broad consensus was established which supported the concept that specific receptor-targeted pharmacotherapy was a biological and clinical tool of considerable relevance in the management of neoplastic disease. In this respect, somatostatin was recognized as the primogenitor of an important and novel class of diagnostic and therapeutic agents.
Irvin M. Modlin