Targeting PI3K/mTOR signaling exerts potent antitumor activity in pheochromocytoma in vivo

Pheochromocytomas (PCC) are mostly benign tumors, amenable to complete surgical resection. However, 1017% of cases can become malignant, and once metastasized, there is no curative treatment for this disease. Given the need to identify effective therapeutic approaches for PCC, we evaluated the antitumor potential of the dual PI3K/mTOR inhibitor BEZ235 against these tumors. We employed an in vivo model of endogenous PCCs (MENX mutant rats), which closely recapitulate the human tumors. Mutant rats with PCCs were treated with 2 doses of BEZ235 (20 and 30 mg/kg), or with placebo, for 2 weeks. Treatment with BEZ235 induced cytostatic and cytotoxic effects on rat PCCs, which could be appreciated by both staining the tumors ex vivo with appropriate markers, and non-invasively by functional imaging (diffusion weighted-DW-MRI) in vivo.

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Lee M, Minaskan N, Wiedemann T, Irmler M, Beckers J, Yousefi BH, Kaissis G, Braren R, Laitinen I, Pellegata NS