Objetivo The goal of this proposal is to investigate the role of tumor microenvironment in metastatic hormone-refractory prostate cancer (mHRPC). Prostate Cancer (PC) is the most common malignancy in men in Europe while mHRPC is the most lethal form of the disease, causing over 95% of PC related deaths. Extensive clinical and preclinical research using state-of-the-art tumour models has led to the development of several new therapeutics that, unfortunately, provide only marginal patient benefit. One key element missing in standard preclinical models is the relevant metastasis microenvironment associated with mHRPC that may dramatically affect disease outcome. Here, I plan to significantly advance our understanding in mHRPC associated microenvironment with the first androgen dependent PC bone metastasis model I developed that mimics both the pathology and disease progression in patients. My preliminary data indicate that metastasis associated stromal cells may form a unique bone metastasis microenvironment that promotes mHRPC. I aim to identify the underlying molecular mechanisms using a multidisciplinary approach combining intra-vital microscopy, dynamic ADT resistance reporter system, innovative adoptive transfer approach and genetic tools of lineage specific knockout. This work is also designed to translate findings made in mouse models into human disease using innovative humanized in vivo models of mHRPC. The findings generated in this project will lead to innovative therapeutic approaches that can effectively treat mHRPC thus relieve this lethal threat on European societies. MetResistance will make a step change in the field of cancer medicine research by providing new standards to study therapy resistance of metastatic cancer an area representing the number one challenge in cancer research and patient care. Ámbito científico medical and health sciencesclinical medicineoncologyprostate cancernatural sciencesphysical sciencesopticsmicroscopymedical and health sciencesbasic medicinepathology Palabras clave tumour microenvironment macrophage mesenchymal stem cell Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-2016-STG - ERC Starting Grant Convocatoria de propuestas ERC-2016-STG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-STG - Starting Grant Institución de acogida THE UNIVERSITY OF EDINBURGH Aportación neta de la UEn € 1 498 176,00 Dirección OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Reino Unido Ver en el mapa Región Scotland Eastern Scotland Edinburgh Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 498 176,00 Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo THE UNIVERSITY OF EDINBURGH Reino Unido Aportación neta de la UEn € 1 498 176,00 Dirección OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Ver en el mapa Región Scotland Eastern Scotland Edinburgh Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 498 176,00