Q3137704 (Q3137704): Difference between revisions
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(Created claim: summary (P836): Cholangiocarcinoma (CCA) is a very aggressive tumor of increasing incidence. Most patients are diagnosed in advanced disease stages and are not eligible for surgery. Early diagnosis of CAC is complex, and available biomarkers do not perform optimally. On the other hand, CCA is very resistant to chemotherapy, with treatment options for patients with very limited advanced disease. Therefore the clinical and therapeutic management of these patients...) |
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Cholangiocarcinoma (CCA) is a very aggressive tumor of increasing incidence. Most patients are diagnosed in advanced disease stages and are not eligible for surgery. Early diagnosis of CAC is complex, and available biomarkers do not perform optimally. On the other hand, CCA is very resistant to chemotherapy, with treatment options for patients with very limited advanced disease. Therefore the clinical and therapeutic management of these patients is not fully resolved. In this multidisciplinary project we propose the twofold objective of: I) identify new markers of the disease, and ii) characterise potential therapeutic targets not yet explored in these tumors. The new markers will be identified in a prospective proteomic and metabolomic pilot study of bile samples from patients. They will then be quantified by direct determination in these samples and in additional samples, and tested in an experimental CEC model. Their presence will also be evaluated in serum samples. The potential new therapeutic targets covered by this project are enzymes regulating epigenetic machinery: histone methyltransferase G9a, DNA methyltransferase 1, and histone deacetylase 1 and 6. Our preliminary observations support the antitumoral potential to inhibit these enzymes not only in CCA cells, but also in liver myofibroblasts responsible for the important oestromal component of these tumors. We will address the study of these epigenetic targets through their genetic and pharmacological inhibition in in vitro and in vivo models of CCA, using inhibitory molecules with novel mechanisms of action generated in our institution. (English) | |||||||||||||||
| Property / summary: Cholangiocarcinoma (CCA) is a very aggressive tumor of increasing incidence. Most patients are diagnosed in advanced disease stages and are not eligible for surgery. Early diagnosis of CAC is complex, and available biomarkers do not perform optimally. On the other hand, CCA is very resistant to chemotherapy, with treatment options for patients with very limited advanced disease. Therefore the clinical and therapeutic management of these patients is not fully resolved. In this multidisciplinary project we propose the twofold objective of: I) identify new markers of the disease, and ii) characterise potential therapeutic targets not yet explored in these tumors. The new markers will be identified in a prospective proteomic and metabolomic pilot study of bile samples from patients. They will then be quantified by direct determination in these samples and in additional samples, and tested in an experimental CEC model. Their presence will also be evaluated in serum samples. The potential new therapeutic targets covered by this project are enzymes regulating epigenetic machinery: histone methyltransferase G9a, DNA methyltransferase 1, and histone deacetylase 1 and 6. Our preliminary observations support the antitumoral potential to inhibit these enzymes not only in CCA cells, but also in liver myofibroblasts responsible for the important oestromal component of these tumors. We will address the study of these epigenetic targets through their genetic and pharmacological inhibition in in vitro and in vivo models of CCA, using inhibitory molecules with novel mechanisms of action generated in our institution. (English) / rank | |||||||||||||||
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| Property / summary: Cholangiocarcinoma (CCA) is a very aggressive tumor of increasing incidence. Most patients are diagnosed in advanced disease stages and are not eligible for surgery. Early diagnosis of CAC is complex, and available biomarkers do not perform optimally. On the other hand, CCA is very resistant to chemotherapy, with treatment options for patients with very limited advanced disease. Therefore the clinical and therapeutic management of these patients is not fully resolved. In this multidisciplinary project we propose the twofold objective of: I) identify new markers of the disease, and ii) characterise potential therapeutic targets not yet explored in these tumors. The new markers will be identified in a prospective proteomic and metabolomic pilot study of bile samples from patients. They will then be quantified by direct determination in these samples and in additional samples, and tested in an experimental CEC model. Their presence will also be evaluated in serum samples. The potential new therapeutic targets covered by this project are enzymes regulating epigenetic machinery: histone methyltransferase G9a, DNA methyltransferase 1, and histone deacetylase 1 and 6. Our preliminary observations support the antitumoral potential to inhibit these enzymes not only in CCA cells, but also in liver myofibroblasts responsible for the important oestromal component of these tumors. We will address the study of these epigenetic targets through their genetic and pharmacological inhibition in in vitro and in vivo models of CCA, using inhibitory molecules with novel mechanisms of action generated in our institution. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 13:05, 12 October 2021
Project Q3137704 in Spain
| Language | Label | Description | Also known as |
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| English | No label defined |
Project Q3137704 in Spain |
Statements
39,750.0 Euro
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79,500.0 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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FUNDACION PARA LA INVESTIGACION MEDICA APLICADA
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42°49'6.42"N, 1°38'39.34"W
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31201
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El colangiocarcinoma (CCA) es un tumor muy agresivo de creciente incidencia. La mayoría de los pacientes son diagnosticados en estadíos avanzados de la enfermedad y no elegibles para la cirugía. El diagnóstico temprano del CCA es complejo, y los biomarcadores disponibles no presentan un rendimiento óptimo. Por otra parte el CCA es muy resistente a la quimioterapia, siendo las opciones de tratamiento para los pacientes con enfermedad avanzada muy escasas. Por lo tanto el manejo clínico y terapeútico de estos pacientes no está completamente resuelto. En este proyecto multidisciplinar planteamos el doble objetivo de: i) identificar nuevos marcadores de la enfermedad, y ii) caracterizar potenciales dianas terapeúticas aún no exploradas en estos tumores. Los nuevos marcadores serán identificados en un estudio prospectivo piloto proteómico y metabolómico de muestras de bilis de pacientes. Posteriormente se cuantificarán por determinación directa en estas muestras y en muestras adicionales, y serán contrastados en un modelo experimental de CCA. Su presencia se evaluará también en muestras de suero. Las potenciales nuevas dianas terapeúticas objeto de este proyecto son enzimas reguladoras de la maquinaria epigenética: la histona metiltransferasa G9a, la DNA metiltransferasa 1, y las histonas deacetilasas 1 y 6. Nuestras observaciones preliminares apoyan el potencial antitumoral de inhibir estas enzimas no solamente en células de CCA, sino también en miofibroblastos hepáticos responsables del importante componente estromal de estos tumores. Abordaremos el estudio de estas dianas epigenéticas mediante su inhibición genética y farmacológica en modelos in vitro e in vivo de CCA, empleando moléculas inhibidoras con mecanismos de acción novedosos generadas en nuestra institución. (Spanish)
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Cholangiocarcinoma (CCA) is a very aggressive tumor of increasing incidence. Most patients are diagnosed in advanced disease stages and are not eligible for surgery. Early diagnosis of CAC is complex, and available biomarkers do not perform optimally. On the other hand, CCA is very resistant to chemotherapy, with treatment options for patients with very limited advanced disease. Therefore the clinical and therapeutic management of these patients is not fully resolved. In this multidisciplinary project we propose the twofold objective of: I) identify new markers of the disease, and ii) characterise potential therapeutic targets not yet explored in these tumors. The new markers will be identified in a prospective proteomic and metabolomic pilot study of bile samples from patients. They will then be quantified by direct determination in these samples and in additional samples, and tested in an experimental CEC model. Their presence will also be evaluated in serum samples. The potential new therapeutic targets covered by this project are enzymes regulating epigenetic machinery: histone methyltransferase G9a, DNA methyltransferase 1, and histone deacetylase 1 and 6. Our preliminary observations support the antitumoral potential to inhibit these enzymes not only in CCA cells, but also in liver myofibroblasts responsible for the important oestromal component of these tumors. We will address the study of these epigenetic targets through their genetic and pharmacological inhibition in in vitro and in vivo models of CCA, using inhibitory molecules with novel mechanisms of action generated in our institution. (English)
12 October 2021
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Pamplona/Iruña
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Identifiers
PI16_01126
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