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Pharmaco-mimetic analysis of the therapeutic value of Vav-dependent metabolic routes in breast cancer

17th national competition for scientific and technical research

Metabolism and cancer

Senior Researcher : Xosé Ramón García Bustelo

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Research Centre or Institution : Centro de Investigación del Cáncer de Salamanca

Abstract

Tumour cells manipulate their metabolism to generate the energy and basic structural elements that they need to continue growing. These routes are also used to produce secondary messengers which, in turn, mediate the activation of signalling pathways and biological processes that cooperate with the tumoral process. These metabolic changes are activated in the majority of cases by the specific deregulation of proto-oncogenes and tumour suppressor genes. Recent research in our laboratory has revealed that Vav family oncogenes, a group of enzymes involved in the stimulation of GTPasas Rho/Rac, all use stimulation of several metabolic routes including, for example, ribogenesis, metabolite transport through membranes and the anabolism of different types of lipids, nucleotides and other basic cell components. This metabolic component seems to be essential, given that it is present in several Vav-dependent tumours such as those of the breast and skin. In this project we propose to use functional tracking and pharmaco-mimetic approaches to characterise the therapeutic value of this metabolic "core" in primary tumorigenesis and metastasis in breast cancer. The proposed study design will make it possible to obtain a clear view of the participation of these routes in malign processes associated with breast cancer, and above all, to identify therapeutic targets of interest in pre-clinical and clinical tumoral stages. The work will also include in silico approaches to identify genetic signatures with diagnostic value in breast cancer.

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