title: Dysregulation of the Met pathway in non-small cell lung cancer: implications for drug targeting and resistance.
abstract: The receptor tyrosine kinase, Met, orchestrates a complex signalling network that physiologically drives a programme of 'invasive growth'. In cancer however, this process may be co-opted to promote proliferation, survival and metastasis of cancer cells. Met is thus a key therapeutic target, not least in non-small cell lung cancer (NSCLC) where it is one of the most commonly dysregulated driver oncogenes. Identifying robust biomarkers that allow the selection of patients most likely to respond to Met targeted therapies will however be essential to realising their potential. This has been underlined recently by the early termination of three pivotal phase III trials investigating Met targeted agents in NSCLC, all of which failed to show clinical benefit. In contrast to these trials, which were relatively unselective, a couple of early phase trials have recently been instigated that select patients on the basis of Met amplification. While still at an early stage, interim results are relatively encouraging and strengthen the rationale for using Met amplifaction as a biomarker. Here we will discuss this and other aberrations in Met signalling in relation to their significance in the therapeutic targeting of Met.
authors.affiliation: 1 Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK ; 2 Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK .
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Sacco
authors.affiliation: 1 Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK ; 2 Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK .
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clague
keywords: Hepatocyte growth factor (HGF); Met; epidermal growth factor receptor (EGFR); lung cancer; non-small cell lung cancer (NSCLC)