Metabolomic analysis of clinical samples to identify response biomarkers and mechanisms of resistance acquired to new therapies targeting lung cancer (Q3138270): Difference between revisions

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(‎Created claim: summary (P836): The overall objective of this project is to identify, through metabolomic and lipidomic analysis, non-invasive biomarkers in response to new therapies directed against lung cancer, and to study metabolic reprogramming associated with the acquisition of resistance. To this end, we propose the analysis of biopsies of tumor tissue and plasma/serum of patients diagnosed with non-small cell lung carcinoma (NCP) from different centers in the Valencian...)
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Metabolomic analysis of clinical samples to identify response biomarkers and mechanisms of resistance acquired to new therapies targeting lung cancer

Revision as of 12:33, 12 October 2021

Project Q3138270 in Spain
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English
Metabolomic analysis of clinical samples to identify response biomarkers and mechanisms of resistance acquired to new therapies targeting lung cancer
Project Q3138270 in Spain

    Statements

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    68,500.0 Euro
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    137,000.0 Euro
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    50.0 percent
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    1 January 2018
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    31 March 2021
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    FUNDACION PARA LA INVESTIGACION DEL HOSPITAL UNIVERSITARIO Y POLITECNICO LA FE DE LA CV. INSTITUTO DE INVESTIGACION SANITARIA LA FE
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    39°28'10.96"N, 0°22'34.82"W
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    46250
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    El objetivo general de este proyecto es identificar, mediante análisis metabolómico y lipidómico, biomarcadores no invasivos de respuesta a las nuevas terapias dirigidas contra el cáncer de pulmón, y estudiar la reprogramación metabólica asociada a la adquisición de resistencias. Para ello, planteamos el análisis de biopsias de tejido tumoral y plasma/suero de pacientes diagnosticados con carcinoma pulmonar no microcítico (CPNM) procedentes de distintos centros de la Comunidad Valenciana, que reciben tratamientos con inhibidores de tirosina quinasa (ITQs) dirigidos contra el receptor del factor de crecimiento epidérmico (EGFR) o con inhibidores de puntos de control inmunitario (ICIs). El material biológico será analizado con una plataforma de metabolómica y lipidómica de última generación que proporciona una elevada cobertura metabólica (>2000 metabolitos), que incluye el uso de diferentes espectrómetros de masas (triple cuadrupolo, cuadrupolo-tiempo de vuelo con movilidad iónica) en combinación con distintas técnicas separativas como la cromatografía líquida (LC) y la cromatografía de gases (GC). En cuanto al diseño experimental, proponemos dos abordajes diferentes y complementarios: (i) estudios caso-control para la búsqueda, en biopsia líquida, de biomarcadores capaces de predecir la respuesta a los ITQs (en pacientes de CPNM EGFR mutados) y a los ICIs (en pacientes tratados con anti-PD1 y anti-PDL1); y (ii) un estudio longitudinal para monitorizar la reprogramación metabólica asociada a la resistencia adquirida a los ITQs en muestras seriadas de tejido tumoral y biopsia líquida. Paralelamente, y con el fin de comprobar el impacto funcional de las alteraciones metabólicas identificadas en los pacientes y establecer el posible mecanismo de acción, estudiaremos las alteraciones metabolómicas en modelos celulares de resistencia adquirida a los ITQs. (Spanish)
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    The overall objective of this project is to identify, through metabolomic and lipidomic analysis, non-invasive biomarkers in response to new therapies directed against lung cancer, and to study metabolic reprogramming associated with the acquisition of resistance. To this end, we propose the analysis of biopsies of tumor tissue and plasma/serum of patients diagnosed with non-small cell lung carcinoma (NCP) from different centers in the Valencian Community, who receive treatments with tyrosine kinase inhibitors (ITQs) directed against the epidermal growth factor receptor (EGFR) or with immune control point inhibitors (ICIs). The biological material will be analysed with a state-of-the-art metabolomic and lipidomics platform that provides high metabolic coverage (>2000 metabolites), which includes the use of different mass spectrometers (triple quadrupole, quadrupole-flight time with ion mobility) in combination with different separative techniques such as liquid chromatography (LC) and gas chromatography (GC). Regarding experimental design, we propose two different and complementary approaches: (I) case-control studies for the search, in liquid biopsy, of biomarkers capable of predicting response to ITQs (in mutated EGFR NSCLC patients) and ICIs (in patients treated with anti-PD1 and anti-PDL1); and (ii) a longitudinal study to monitor metabolic reprogramming associated with acquired resistance to ITQs in serial samples of tumor tissue and liquid biopsy. In parallel, and in order to verify the functional impact of the metabolic alterations identified in patients and establish the possible mechanism of action, we will study metabolomic alterations in cell models of resistance acquired to ITQs. (English)
    12 October 2021
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    Valencia
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    Identifiers

    PI17_01282
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