Molecular imaging for detection of sensitivity and resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer

Abstract

Advancing knowledge of non-small cell lung cancer (NSCLC) has provided new treatment options based on the specific gene alterations found in individual tumors. The presence of activating mutations in the epidermal growth factor receptor (EGFR) in NSCLC is strongly associated with a high sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and is also a criterion used to identify candidates for first-line therapy with these drugs among patients with advanced disease. However, acquired resistance to EGFR TKIs invariably emerges over time due in part to secondary mutations in EGFR or redundant lateral signaling. Molecular imaging, allowing the visualization of cellular processes and their modulation by both conventional anticancer drugs and molecularly targeted agents, may be effectively used in NSCLC patients during treatment with EGFR TKIs. In particular, positron emission tomography with 18F-FDG and 18F-FLT has been performed in both preclinical and clinical settings to distinguish treatment-sensitive from treatment-resistant NSCLCs. Here we provide a short overview of the mechanisms underlying sensitivity and resistance of NSCLCs to EGFR TKIs and then focus on the contribution that molecular imaging can make to the development of tailored therapy in NSCLC patients.