Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition
| Autor: | Pascal Croteau, Christian Couture, Mathilde Couetoux du Tertre, Valérie Hindie, Valerie Higenell, Karen Gambaro, Yannick-André Breton, Cyrla Hoffert, Victor Cohen, Lise Tremblay, Maud Marques, Laura McIntosh, Normand Blais, Stephane Parent, Gerald Batist, Hangjun Wang, Alan Spatz, Gwenael Pottiez, Nicole Bouchard, Laetitia Cortes, Vincent Pelsser, Jason Agulnik, Luisa Izzi, Razvan Diaconescu, Suzan McNamara |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Combination therapy Clinical Biochemistry Protein signature NSCLC Proteomics medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Crizotinib Internal medicine medicine Liquid biopsy Molecular Biology Mutation Prediction of response business.industry Research General Medicine 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine Personalized medicine business Tyrosine kinase medicine.drug Blood sampling |
| Zdroj: | Clinical Proteomics |
| ISSN: | 1559-0275 1542-6416 |
| DOI: | 10.1186/s12014-020-9269-6 |
| Popis: | Background ALK tyrosine kinase inhibition has become a mainstay in the clinical management of ALK fusion positive NSCLC patients. Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance. To further refine the application of personalized medicine in this indication, this study aimed to identify prognostic proteomic biomarkers in ALK fusion positive NSCLC patients to crizotinib. Methods Twenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment. Targeted proteomics of 327 proteins using MRM-MS was used to measure plasma levels at baseline (including pre-treatment and early treatment blood samples) and assess potential clinical association. Results Patients were categorized by duration of response: long-term responders [PFS ≥ 24 months (n = 7)], normal responders [3 Conclusion In conjunction with ALK mutation, the expression of this proteomic signature may represent a liquid biopsy-based marker of long-term response to crizotinib in NSCLC. Expanding the utility of prognostic biomarkers of response duration could influence choice of therapy, therapeutic sequencing, and potentially the need for alternative or combination therapy. Trial registration ClinicalTrials.gov, NCT02041468. Registered 22 January 2014, https://clinicaltrials.gov/ct2/show/NCT02041468?term=NCT02041468&rank=1 |
| Databáze: | OpenAIRE |
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