Management of breast cancer: is there a role for somatostatin and its analogs?
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.
Boccardo
F
F
Academic Unit of Medical Oncology, National Cancer Institute, Genoa, Italy. boccardo@hp380.ist.unige.it
Amoroso
D
D
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D013004:Somatostatin