Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients

Autor: Carmela Rodríguez-López, Patricia Mondelo-Macía, Teresa Curiel, Antònia Obrador-Hevia, Laura Muinelo-Romay, Laura Valiña, Silvia Calabuig-Fariñas, Roberto Díaz-Peña, Rafael López-López, Angel Diaz-Lagares, Aitor Azkárate, Óscar Rapado-González, María Mercedes Suárez-Cunqueiro, Luis León-Mateos, Ihab Abdulkader, Alicia Abalo, Jorge García-González, Santiago Aguín
Přispěvatelé: Universidade de Santiago de Compostela. Departamento de Cirurxía e Especialidades Médico-Cirúrxicas
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Male
MET copy number
medicine.medical_treatment
proteínas protooncogénicas c-met
dosificación génica
humanos
resistencia a medicamentos
Drug Resistance
Gene Dosage
circulating free DNA (cfDNA)
MET amplification
Targeted therapy
0302 clinical medicine
Circulating tumor cell
estudios prospectivos
Neoplasms
antineoplásicos
Prospective Studies
lcsh:QH301-705.5
Circulating tumor cells (CTCs)
neoplasias
General Medicine
Proto-Oncogene Proteins c-met
targeted therapy
Neoplastic Cells
Circulating
ErbB Receptors
Cell-free fetal DNA
030220 oncology & carcinogenesis
inhibidores de proteína cinasas
Biomarker (medicine)
Female
MET protein expression
Cell-Free Nucleic Acids
medicine.medical_specialty
circulating tumor cells (CTCs)
estudios de casos y controles
Met amplification
Circulating free DNA (cfDNA)
Antineoplastic Agents
Article
03 medical and health sciences
Internal medicine
medicine
Biomarkers
Tumor
Humans
Liquid biopsy
Protein Kinase Inhibitors
Retrospective Studies
business.industry
Head and neck cancer
estudios retrospectivos
Liquid Biopsy
Cancer
medicine.disease
030104 developmental biology
lcsh:Biology (General)
Drug Resistance
Neoplasm
Case-Control Studies
business
Zdroj: Cells
Minerva: Repositorio Institucional de la Universidad de Santiago de Compostela
Universidad de Santiago de Compostela (USC)
Volume 9
Issue 2
Cells, Vol 9, Iss 2, p 522 (2020)
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname
ISSN: 2073-4409
Popis: 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&minus
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.
Databáze: OpenAIRE
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