Find in Library

MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed <i>MET</i> amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and <i>MET</i> copy number (CN) in cancer patients (<i>r</i> = 0.57, <i>p</i> &lt;10^&#8722;10) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch^&#174; and Parsortix systems and monitored patients under anti-EGFR treatment (<i>n</i> = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of <i>MET</i> CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET⁺ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma <i>MET</i> CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.