Objectif Poor prognosis of cancer results from two central progression events, (i) the intravasation of cancer cells into blood vessels which leads to metastasis to distant organs and ultimately lethal tumor overload and (ii) cancer cell survival and adaptation to metabolic stress which causes resistance to anti-cancer therapy and limits life expectancy. Using a novel multiphoton microendoscope device recently developed by myself and collaborators, I here aim to overcome tissue penetration limits and identify important progression events deeply inside tumors. The hard- and software of the microendoscope will be optimized for automated position control and panoramic rotation to sample large tissue volumes and validated for stability and safety. We then will address the locations and mechanisms inside tumors that: (1) enable tumor-cell migration and penetration into blood vessels for distant metastasis and (2) mediate enhanced tumor-cell survival and resistance to experimental radiation- and chemotherapy. This basic inventory will serve to address (3) whether and how the niches for both intravasation and resistance overlap and connected with microenvironmental triggers, including defective blood vessels, signalling pathways of malnutrition and hypoxia, and tissue damage. The strategies include 3D microscopy of live fluorescent multi-color tumors and molecular reporters to record cancer cell migration, proliferation and death in the context with embedding tissue structures and metabolic signals. Once identified and characterized, (4) the niches and signals inducing intravasation and resistance (i.e. integrin adhesion receptors, cytoskeletal regulators, metabolic signalling) will be exploited as targets to enhance experimental radiation and chemotherapy. Preclinical microendoscopy will deliver new insight into cancer progression further contribute impulses to microendoscopy for disease monitoring in patients (“optical biopsy”). Champ scientifique natural sciencescomputer and information sciencessoftwarenatural sciencesphysical sciencesopticsmicroscopymedical and health sciencesclinical medicineoncology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-CG-2013-LS4 - ERC Consolidator Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2013-CoG Voir d’autres projets de cet appel Régime de financement ERC-CG - ERC Consolidator Grants Institution d’accueil STICHTING RADBOUD UNIVERSITEIT Contribution de l’UE € 1 602 800,00 Adresse HOUTLAAN 4 6525 XZ Nijmegen Pays-Bas Voir sur la carte Région Oost-Nederland Gelderland Arnhem/Nijmegen Type d’activité Higher or Secondary Education Establishments Contact administratif Paul Smits (Prof.) Chercheur principal Peter Friedl (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (3) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire STICHTING RADBOUD UNIVERSITEIT Pays-Bas Contribution de l’UE € 1 602 800,00 Adresse HOUTLAAN 4 6525 XZ Nijmegen Voir sur la carte Région Oost-Nederland Gelderland Arnhem/Nijmegen Type d’activité Higher or Secondary Education Establishments Contact administratif Paul Smits (Prof.) Chercheur principal Peter Friedl (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée GRINTECH GMBH Allemagne Contribution de l’UE € 155 400,00 Adresse SCHILLERSTRASSE 1 07745 Jena Voir sur la carte Région Thüringen Thüringen Jena, Kreisfreie Stadt Type d’activité Private for-profit entities (excluding Higher or Secondary Education Establishments) Contact administratif Torsten Possner (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée LAVISION BIOTEC GMBH Allemagne Contribution de l’UE € 241 800,00 Adresse ASTASTRASSE 14 33617 Bielefeld Voir sur la carte Région Nordrhein-Westfalen Detmold Bielefeld, Kreisfreie Stadt Type d’activité Private for-profit entities (excluding Higher or Secondary Education Establishments) Contact administratif Volker Andresen Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée