Annalisa Ferrotta
Targeting Oncogenic PI3K in Glioblastoma
Abstract
Phosphoinositide 3-kinase (PI3K) signaling is altered in nearly all cases of glioblastoma (GBM), which is a highly aggressive malignant brain tumor in adults with bleak prognosis. Despite promising preclinical evidence, PI3K inhibitors have universally failed in GBM clinical trials. A recent new wave in PI3K inhibitors with improved pharmacological properties and novel mechanisms of action warrants a reinvestigation of targeting this pathway in GBM. Here I propose to investigate mediators of resistance to PI3K pathway inhibition in GBM identified by genome wide CRISPR knockout screens. In parallel, I will characterize the pharmacodynamics and efficacy of next-generation PI3K inhibitors in patient derived models of GBM ex vivo and in vivo. This work will elucidate the contribution of the PI3K signaling network in GBM progression and identify novel therapeutic approaches with PI3K inhibitors for more effective treatments in GBM.
I am incredibly grateful for the support from the PhRMA Foundation to advance therapeutic development for glioblastoma, a devastating disease with no effective treatment options. In addition to connecting me to a network of renowned scientists, this fellowship empowers my research to push the boundaries of innovation with the ultimate goal of improving patient outcome.
