1. Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients.
- Author
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Mondelo-Macía P, Rodríguez-López C, Valiña L, Aguín S, León-Mateos L, García-González J, Abalo A, Rapado-González O, Suárez-Cunqueiro M, Díaz-Lagares A, Curiel T, Calabuig-Fariñas S, Azkárate A, Obrador-Hevia A, Abdulkader I, Muinelo-Romay L, Diaz-Peña R, and López-López R
- Subjects
- Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Case-Control Studies, Drug Resistance, Neoplasm genetics, ErbB Receptors antagonists & inhibitors, Female, Humans, Liquid Biopsy, Male, Neoplasms drug therapy, Neoplasms pathology, Prospective Studies, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Retrospective Studies, Cell-Free Nucleic Acids blood, Gene Dosage, Neoplasms blood, Neoplasms genetics, Neoplastic Cells, Circulating metabolism, Proto-Oncogene Proteins c-met blood, Proto-Oncogene Proteins c-met genetics
- Abstract
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 MET 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 MET copy number (CN) in cancer patients ( r = 0.57, p <10
-10 ) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch® and Parsortix systems and monitored patients under anti-EGFR treatment ( n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET 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 MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.- Published
- 2020
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