Combined Therapy with RAD001 e BEZ235 Overcomes Resistance of PET Cells to mTOR Inhibition

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Introduction: Since the PI3K/Akt/mTOR proliferation axis is often deregulated in PETs, the mTORC1 complex inhibitor Everolimus (RAD001) represents an effective treatment for PETs. However, RAD001 leads to a re-activation of PI3K activity and phosphorylation of Akt, which may promote resistance to the treatment. Thus, direct inhibition of PI3K may represent a novel potential target for PETs.

Aim(s): To test PI3K inhibitors in models of responsiveness or resistance (primary and secondary) to RAD001.

Materials and methods: Three novel PI3K inhibitors (BEZ235, BKM120 and BYL719) were evaluated on BON-1 (50-60% of inhibition of cell proliferation caused by RAD001) and QGP-1 (primarily unresponsive to RAD001) cells and on BON-1 cells acquiring a secondary resistance.

Conference: 11th Annual ENETSConcerence (2014)

Presenting Author:

Authors: Passacantilli I, Capurso G, Archibugi L, Calabretta S, Delle Fave G,

Keywords: mTOR, PI3K, resistance,

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