Combined treatment with MET inhibitors and other therapies in lung cancer

Molecular targeted therapy has made significant progress in human cancers in the past decade and has become an integral part of modern human cancer treatment. Targeted drugs are now moving closer to be used in tailored therapy with personalized molecular predictive biomarkers assay development to couple with the therapeutics. Much progress has been made in non-small cell lung cancer (NSCLC) using the tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib to target the epidermal growth factor receptor (EGFR) clinically in patients with advanced disease (1). However, the long term efficacy of the TKIs is still inevitably limited, as patients with NSCLC who initially have primary tumor response, always develop acquired resistance against EGFR-TKI monotherapy typically after 6-12 months of treatment (2). Recent research studies to elucidate mechanisms of acquired EGFR TKI resistance identified alternative molecular targets of receptor tyrosine kinases (RTKs) to be responsible, such as AXL (3), as well as MET receptor (4) and its natural ligand hepatocyte growth factor (HGF) (5), as implicated in mediating the tumor escape process.