Epigenetic mechanisms of resistance to castration in prostate cancer: therapeutic opportunities in combination with androgen receptor antagonists. (Q3137594): Difference between revisions
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(Created claim: summary (P836): Therapeutic resistance represents the leading cause of cancer death and pharmaceutical expenditure in cancer care. Researching the cellular and molecular mechanisms associated with the acquisition of resistance is of vital importance for the clinical management of patients and in the management of resources of public health systems. Prostate cancer is paradigmatic of this situation; while 5-year survival of patients with early-stage tumors is ab...) |
(Changed label, description and/or aliases in en: translated_label) |
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Epigenetic mechanisms of resistance to castration in prostate cancer: therapeutic opportunities in combination with androgen receptor antagonists. | |||
Revision as of 12:35, 12 October 2021
Project Q3137594 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Epigenetic mechanisms of resistance to castration in prostate cancer: therapeutic opportunities in combination with androgen receptor antagonists. |
Project Q3137594 in Spain |
Statements
45,750.0 Euro
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91,500.0 Euro
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50.0 percent
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1 January 2017
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31 March 2020
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INSTITUTO DE INVESTIGACION BIOMEDICA DE BELLVITGE
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41°21'35.50"N, 2°5'59.24"E
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08101
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La resistencia terapéutica representa la principal causa de muerte por cáncer y de gasto farmacéutico en la atención oncológica. Investigar pues los mecanismos celulares y moleculares asociados a la adquisición de resistencia es de vital importancia para el manejo clínico de los pacientes y en la gestión de recursos de los sistemas públicos de salud. El cáncer de próstata es paradigmático de esta situación; mientras la supervivencia a los 5 años de los pacientes con tumores en estadios iniciales es de cerca del 100%, esta baja al 25% en pacientes con enfermedad metastásica, que casi invariablemente desarrollan un fenotipo agresivo, resistente a la castración y altamente invasivo. Este proyecto quiere dilucidar la contribución de la desregulación del epigenoma y la modificación de la estructura de la cromatina a la adquisición de resistencia a terapias antiandrogénicas. Para ello, (i) utilizaremos modelos de ingenieria genética que mimetizan la carcinogenesis que ocurre en los pacientes, incluidas el origen en las células del epitelio prostático y las mutaciones causales mas frecuentes en humanos, Nkx3.1, Pten y Tp53; (ii) realizaremos estudios de accesibilidad de la cromatina y regulación de la expression génica in vivo y in vitro mediante técnicas secuenciación y ensayos funcionales en contextos de respuesta y resistencia al tratamiento con antagonistas del receptor de andrógenos; (iii) llevaremos a cabo ensayos preclínicos destinados a evaluar el potencial terapéutico de tratamientos combinados de anti-andrógenos con fármacos epigenéticos; y finalmente, (iv) validaremos el potencial valor pronóstico de biomarcadores identificados mediante el uso de tissue microarrays y de predicción de respuesta en muestras de biopsia liquida. (Spanish)
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Therapeutic resistance represents the leading cause of cancer death and pharmaceutical expenditure in cancer care. Researching the cellular and molecular mechanisms associated with the acquisition of resistance is of vital importance for the clinical management of patients and in the management of resources of public health systems. Prostate cancer is paradigmatic of this situation; while 5-year survival of patients with early-stage tumors is about 100 %, it is reduced to 25 % in patients with metastatic disease, who almost invariably develop an aggressive, castration-resistant and highly invasive phenotype. This project aims to elucidate the contribution of deregulation of the epigenoma and the modification of the structure of chromatin to the acquisition of resistance to antiandrogenic therapies. To this end, (i) we will use models of genetic engineering that mimic the carcinogenesis that occurs in patients, including the origin in prostate epithelium cells and the most common causal mutations in humans, Nkx3.1, Pten and Tp53; (II) conduct chromatin accessibility studies and regulation of gene expression in vivo and in vitro using sequencing techniques and functional assays in response and resistance contexts with androgen receptor antagonists; (III) conduct preclinical trials to assess the therapeutic potential of combination anti-androgen treatments with epigenetic drugs; and finally, (iv) we will validate the potential prognostic value of biomarkers identified through the use of tissue microarrays and response prediction in liquid biopsy samples. (English)
12 October 2021
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Hospitalet de Llobregat, L'
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Identifiers
PI16_01070
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