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

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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.

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Acknowledgments

F.G. sincerely thanks the Italian Society of Endocrinology for awarding with the “Premio SIE 35”, as Best Young Researcher in 2017.

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  1. Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi, 10, 16132, Genoa, Italy

    F. Gatto & D. Ferone

  2. Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy

    F. Gatto, M. Arvigo & D. Ferone

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F.G. received fees for lectures and/or participation to advisory boards for Novartis, AMCo, and IONIS Pharmaceuticals. D.F. received grants and fees for lectures and participation to advisory boards for Novartis, Ipsen and Pfizer. M.A. has nothing to disclose.

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Gatto, F., Arvigo, M. & Ferone, D. Somatostatin receptor expression and patients’ response to targeted medical treatment in pituitary tumors: evidences and controversies. J Endocrinol Invest 43, 1543–1553 (2020). https://doi.org/10.1007/s40618-020-01335-0

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