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Gulde, S. ; Wiedemann, T. ; Schillmaier, M.* ; Valença, I. ; Lupp, A.* ; Steiger, K.* ; Yen, H.Y.* ; Bäuerle, S.* ; Notni, J.* ; Luque, R.* ; Schmid, H.* ; Schulz, S.* ; Ankerst, D.P.* ; Schilling, F.* ; Pellegata, N.S.

Gender-specific efficacy revealed by head-to-head comparison of pasireotide and octreotide in a representative in vivo model of nonfunctioning pituitary tumors.

Cancers 13:3097 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail against NFPTs. Thus, identifying effective therapies is clinically relevant. As NFPTs express SSTR3 at high levels, pasireotide, a multireceptor-targeted SSA, might be beneficial. Here we evaluated pasireotide in the only representative model of spontaneous NFPTs (MENX rats) in vivo. Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. While tumors in placebo-treated rats increased in volume over time, PTs in drug-treated rats displayed significant growth suppression, and occasional tumor shrinkage. Pasireotide elicited stronger growth inhibition. Radiological responses correlated with tumors’ proliferation rates. Both SSAs, but especially pasireotide, were more effective in female vs. male rats. Basal Sstr3 expression was significantly higher in the former group. It is noteworthy that female human NFPTs patients also have a trend towards higher SSTR3 expression. Altogether, our studies provide the rationale for testing pasireotide in patients with residual/recurrent NFPTs. If confirmed, the sex-related SSTR3 expression might be used as criteria to stratify NFPTs patients for treatment with pasireotide.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mri ; Nonfunctioning Pituitary Tumors ; Octreotide ; Pasireotide ; Sex Differences In Drug Response ; Somatostatin Receptors; Somatostatin Receptors; Adenomas; Expression; Management; Growth
ISSN (print) / ISBN 2072-6694
Zeitschrift Cancers
Quellenangaben Band: 13, Heft: 12, Seiten: , Artikelnummer: 3097 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)
Förderungen Wilhelm Sander Stiftung foundation
Deutsche Krebshilfe
German Research Foundation (Deutsche Forschungsgemeinschaft-DFG)