Identification of vulnerabilities in triple-negative breast cancer: analysis of clonal heterogeneity of tumor subpopulations (Q3137700): Difference between revisions

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(‎Created claim: summary (P836): Currently, a high percentage of patients with breast cancer is not cured, which makes it necessary to discover new molecular alterations that can be pharmacologically inhibited. In preliminary studies using functional transcriptomic analysis, our group has identified relevant genes in triple-negative breast cancer, such as some transcription factors (LM04, DEPDC, FOXM1) or kinases involved in mitosis (NIMA and CDCA3). In this project we want to...)
(‎Changed label, description and/or aliases in en: translated_label)
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Identification of vulnerabilities in triple-negative breast cancer: analysis of clonal heterogeneity of tumor subpopulations

Revision as of 13:05, 12 October 2021

Project Q3137700 in Spain
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English
Identification of vulnerabilities in triple-negative breast cancer: analysis of clonal heterogeneity of tumor subpopulations
Project Q3137700 in Spain

    Statements

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    94,000.0 Euro
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    117,500.0 Euro
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    80.0 percent
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    1 January 2017
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    31 March 2020
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    SECRETARIA GENERAL DEL SERVICIO DE SALUD DE CASTILLA-LA MANCHA
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    38°59'42.32"N, 1°51'21.31"W
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    02003
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    En la actualidad, un alto porcentaje de pacientes con cáncer de mama no se cura, lo que hace necesario el descubrimiento de nuevas alteraciones moleculares que puedan ser inhibidas farmacológicamente. En estudios preliminares usando análisis transcriptomico funcional, nuestro grupo ha identificado genes relevantes en cáncer de mama triple negativo, como son algunos factores de transcripción (LM04, DEPDC, FOXM1) o quinasas implicadas en mitosis (NIMA y CDCA3). En este proyecto queremos profundizar en el mecanismo de acción de estos genes en relación a su contribución oncogénica. Objetivos: 1. Estudiar la función oncogénica de los factores de transcripción LM04, DEPDC, FOXM1. 2. Estudiar la función oncogénica de las quinasas de mitosis NIMA y CDCA3. 3. Identificar compuestos que inhiban la función de los productos de estos genes. 4. Identificar mecanismos de synthetic lethality en modelos con expresión reducida de estos genes. 5. Identificar modelos de resistencia primaria y crear modelos de resistencia secundaria a inhibidores de bromodomain. Metodología: siRNA de LM04, DEPDC, FOXM1, NIMA y CDCA3. Estudios de proliferación, migración, western-blot, librerías farmacológicas, análisis transcriptómico, generación modelos resistentes, modelos in vivo, etc. A high percentage of breast cancer patients are not currently cured, what forces the discovery of new molecular alterations that can be inhibited pharmacologically. In preliminary studies using transcriptomic analyses, our group have identified relevant genes in triple negative breast cancer, some are transcription factors (LM04, DEPDC, FOXM1) or kinases implicated in mitosis (NIMA y CDCA3). In this project we pretend to evaluate the mechanism of action of these genes in relation to their role in the oncogenesis of triple negative breast cancer. Objectives: 1. To study the function of oncogenic transcription factors (LM04, DEPDC, FOXM1). 2. To study the function of kinases involved in mitosis (NIMA y CDCA3). (Spanish)
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    Currently, a high percentage of patients with breast cancer is not cured, which makes it necessary to discover new molecular alterations that can be pharmacologically inhibited. In preliminary studies using functional transcriptomic analysis, our group has identified relevant genes in triple-negative breast cancer, such as some transcription factors (LM04, DEPDC, FOXM1) or kinases involved in mitosis (NIMA and CDCA3). In this project we want to deepen the mechanism of action of these genes in relation to their oncogenic contribution. Objectives: 1. Study the oncogenic function of transcription factors LM04, DEPDC, FOXM1. 2. Study the oncogenic function of NIMA and CDCA3 mitosis kinases. 3. Identify compounds that inhibit the function of the products of these genes. 4. Identify mechanisms of synthetic Lethality in models with reduced expression of these genes. 5. Identify primary resistance models and create models of secondary resistance to bromodomain inhibitors. Methodology: siRNA of LM04, DEPDC, FOXM1, NIMA and CDCA3. Proliferation studies, migration, western-blot, pharmacological libraries, transcriptomic analysis, generation resistant models, in vivo models, etc. A high percentage of breast cancer patients are not currently cured, what forces the discovery of new molecular alterations that can be inhibited pharmacologically. In preliminary studies using transcriptomic analyses, our group have identified relevant genes in triple negative breast cancer, some are transcription factors (LM04, DEPDC, FOXM1) or kinases implicated in mitosis (NIMA and CDCA3). In this project we intend to evaluate the mechanism of action of these genes in relation to their role in the oncogenesis of triple negative breast cancer. Objectives: 1. To study the function of oncogenic transcription factors (LM04, DEPDC, FOXM1). 2. To study the function of kinases involved in mitosis (NIMA and CDCA3). (English)
    12 October 2021
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    Albacete
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    Identifiers

    PI16_01121
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