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

Abstract

Background Somatostatin receptors (SSTs) are widely co-expressed in pituitary tumors. SST₂ and SST₅ 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 SST₅ 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 SST₂ expression in somatroph tumors directly correlates with GH and IGF-1 decrease after first-generation SRL treatment. SST₂ immunohistochemistry represents a valuable tool to predict biochemical response to first-generation SRLs in acromegalic patients. Pasireotide seems to exert its biological effects via SST₂ in unselected patients. However, in those subjects resistant to first-generation SRLs, harbouring tumors with negligible SST₂ 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 SST₂ 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.