Somatostatin receptor expression and patients' response to targeted medical treatment in pituitary tumors: evidences and controversies

Background Somatostatin receptors (SSTs) are widely co-expressed in pituitary tumors. SST(2)and SST(5)are the most represented SST subtypes. First-generation somatostatin receptor ligands (SRLs) mainly target SST2, while pasireotide, a multi-receptor ligand, shows high binding affinity for both SST(5)and SST2. Therefore, SRLs are routinely used as medical treatment for GH-, TSH-, and ACTH-secreting pituitary tumors. Methods Critical revision of literature data correlating SST expression with patients' response to SRLs. Results SST(2)expression in somatroph tumors directly correlates with GH and IGF-1 decrease after first-generation SRL treatment. SST(2)immunohistochemistry represents a valuable tool to predict biochemical response to first-generation SRLs in acromegalic patients. Pasireotide seems to exert its biological effects via SST(2)in unselected patients. However, in those subjects resistant to first-generation SRLs, harbouring tumors with negligible SST(2)expression, pasireotide can act throughout SST5. More than somatotroph tumors, TSH-omas represent the paradigm of tumors showing a satisfactory response to SRLs. This is probably due to the high SST(2)expression observed in nearly 100% of cases, as well as to the balanced amount of SST5. In corticotroph tumors, pasireotide mainly act via SST5, although there is a need for translational studies correlating its efficacy with SST expression in this peculiar tumor histotype. Conclusions The assumption more target receptor, more drug efficacy is not straightforward for SRLs. The complex pathophysiology of SSTs, and the technical challenges faced to translate research findings into clinical practice, still need our full commitment to make receptor evaluation a worthwhile procedure for individualizing treatment decisions.