Endocrine Abstracts

Introduction: 15% of pituitary tumors are considered as aggressive based on resistance to conventional treatment. Less than 40% of these cases respond to temozolomide treatment underlining the need for new therapeutic options. The PI3K/Akt/mTOR pathway, upregulated in different pituitary tumors subtypes, can be targeted by different drugs in particular BKM 120, a pure PI3K inhibitor, and BEZ235, a dual PI3K/mTOR inhibitor.

Objective: To study the anti-tumoral effect of BKM120 and BEZ235, on a model of rat prolactin pituitary tumor SMtTW-3.

Method: One-month after grafted SMtTW3 rats were treated via oral gavage 5 days/week with BKM120 (5 mg/kg per day, 20 days; n=15) or BEZ235 (20 mg/kg per day, 15 days (n=13) or 30 days (n=13)) or control (n=10 for each treatment). Antitumoral effect was evaluated by measuring tumor weigh at sacrificed and prolactin plasma level was measured before and after treatment. Ki67 index, mitosis were calculated on tumor section.

Results: BKM120 treatment reduces significantly tumor growth and prolactin secretion compare to controls with a final tumor weight of 5.36±2.27 vs 28.76±7.50 g (P<0.001) and prolactin concentration of 1909±234.6 vs 5465±1026 μg/l.

BEZ235 treatment was less efficient and reduced tumor growth only after 30 days compare to control (35.87±16.40 vs 47.52±8.69 g; P<0.05) and did not significantly decrease tumor growth after 15 days (10.89±4.06 vs 11.86±5.83 g) or prolactin secretion after 15 or 30 days of treatment (respectively 6718±3687 vs 7183±4452 μg/l and 6846±3676 vs 8275±4323 μg/l).

Both treatments were associated with a decrease of ki67 index and mitosis compared to tumors in control group.

Conclusion: BKM120, a pure PI3K inhibitor, present promising result for treating patient with aggressive pituitary tumor resistant to any conventional treatment. Differential effect between BKM120 and BEZ235 on tumor growth and PI3K/AKT/mTOR pathway is under investigation.