Tumor response to a given therapeutic regimen depends on many factors including the specific molecular signature or gene expression profile of an individual tumor, the characteristics of tumor microenvironment and some host-related factors. A number of traditional biomarkers are currently used to guide physicians in therapeutic decisions and new molecular tests are becoming increasingly available to identify individual tumor aggressiveness, sensitivity or resistance to therapy and risk of tumor relapse and metastases. In this framework our research activity is focused on the development and validation of innovative imaging modalities that allow 1) the non-invasive visualization of biological processes that characterize an individual tumor; 2) the in vivo detection of molecular target expression so that patients can be selected for targeted therapy; 3) the prediction and early detection of tumor response to conventional and targeted therapy; 4) the non-invasive identification of resistant tumors ; 5) imaging-guided adaptation of therapy in the individual patient. Recently we investigated early changes of the 18F-FDG uptake in response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). We found that the effective inhibition of EGFR signaling in NSCLC causes an early metabolic switch from aerobic glycolysis to mitochondrial oxidative phosphorylation both in vitro and in vivo. The reduction of glycolysis was mediated by the ERK 1/2 dependent reduction of HKII and p-PKM2 (Tyr105) whereas the reactivation of oxidative phosphorylation occurred through the AKT dependent upregulation of mitochondrial complexes. The consequent increase of ATP levels and reduction of lactate secretion will ultimately improve NSCLC sensitivity to chemotherapy and radiation therapy.
|▼ Translational Molecular Imaging in Cancer|