Somatostatin and related
peptides are a family of
peptides which are ubiquitous and function as endogenous
growth inhibitors. Analogs have been developed through the introduction of a D-
amino acid in the position 8 of
somatostatin moiety which is more resistant to the action of endogenous
peptidases than the parental moiety. Both
somatostatin and its analogs interact with specific receptors on the cell surface. The five receptor subtypes, SSTR-1 to SSTR-5, which have been characterized so far, have a different affinity for
somatostatin and its analogs. This and the fact that receptors are not homogeneously expressed in tissues account for the different activity of these compounds, all of which have demonstrated tumoristatic properties both in vitro and in vivo. The interaction of
somatostatin and of
somatostatin analogs with specific SSTR receptors is crucial to the antiproliferative mechanisms exerted by these compounds in vitro and in some animal models and the various pathways have been reviewed in detail. However, inhibition of angiogenesis and suppression of lactogenic
hormones might represent alternative mechanisms, in particular in
breast cancer. The rationale for the use of
somatostatin and its analogs in
breast cancer patients and to combine these
peptides with antihormones, like
antiestrogens or
prolactin-lowering drugs, or cytotoxics has been reviewed together with the results obtained in phase II and comparative trials. The reasons for the limited efficacy shown by these compounds either when used alone or when used in combination with other drugs have also been critically reviewed in the perspective of new trials.