RT Journal Article
T1 Gender-Specific Efficacy Revealed by Head-to-Head Comparison of Pasireotide and Octreotide in a Representative In Vivo Model of Nonfunctioning Pituitary Tumors.
A1 Gulde, Sebastian
A1 Wiedemann, Tobias
A1 Schillmaier, Mathias
A1 Valença, Isabel
A1 Lupp, Amelie
A1 Steiger, Katja
A1 Yen, Hsi-Yu
A1 Bäuerle, Stephen
A1 Notni, Johannes
A1 Luque, Raul
A1 Schmid, Herbert
A1 Schulz, Stefan
A1 Ankerst, Donna P
A1 Schilling, Franz
A1 Pellegata, Natalia S
K1 MRI
K1 nonfunctioning pituitary tumors
K1 octreotide
K1 pasireotide
K1 sex differences in drug response
K1 somatostatin receptors
AB 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.
SN 2072-6694
YR 2021
FD 2021-06-21
LK https://hdl.handle.net/10668/25805
UL https://hdl.handle.net/10668/25805
LA en
DS RISalud
RD Apr 8, 2025