University of Cincinnati
School of Medicine
Young Investigator Grant

NANETS congratulates Hala Elnakat Thomas as the 2013 Young Investigator Grant Recipient for her work on mTOR inhibition in the treatment of pNETs.

Because the allosteric inhibitor of the mammalian Target Of Rapamycin (mTOR), everolimus (RAD001), has already shown efficacy in pancreatic neuroendocrine tumors (pNETs), it is compelling to assess in this indication, the ability of the next-generation mTOR inhibitors to impede tumor progression. Toward this end, BEZ235 a dual phosphatidylinositide-3OH kinase (PI3K)/mTOR inhibitor is currently being evaluated as a single agent in a number of phase I/II clinical trials for treatment of patients with pNETs either prior to or after failure of allosteric mTOR inhibitors. Based on my previous work, I predict that a major benefit of treating pNETs with RAD001 in combination with BEZ235 will be a synergistic inhibition of mTOR at lower doses of each drug, which will increase specificity while decreasing toxicity. The preclinical data generated from this award will not only improve our molecular and mechanistic understanding of the drug combination but will more importantly potentially improve the clinical outcome for pNET patients treated with RAD001 and BEZ235 in combination in lieu of either drug as a single agent.