Humsa S.
Venkatesh1, Charles D. James2, Daphne A. Haas-Kogan2,
Sabrina M. Ronen1
1Radiology and Biomedical Imaging,
University of California, San Francisco, San Francisco, CA, United States; 2Neurological
Surgery, University of California, San Francisco
As
the PI3K pathway is activated in 88% of glioblastomas, it is the target of
several novel therapies. The purpose of this investigation is to study GBM
cells with different genetic backgrounds in order to establish hyperpolarized
lactate and PC as biomarkers of PI3K inhibition. Two inhibitors of PI3K
signaling and agents that do not affect signaling were investigated.
Hyperpolarized lactate and PC dropped only when signaling was inhibited and
this observation was mechanistically linked to a drop in HIF-1, which
controls expression of LDH and choline kinase. This suggests an application
for these metabolites as noninvasive biomarkers for PI3K-targeted anticancer
treatments.