Objective The tumour microenvironment or niche is the vital non-cancerous compartment of the tumour structure. Thus, targeting its tissue-derived cells represents a promising avenue to better therapeutic interventions. However, knowledge about the tissue cells taking part of the tumour niche during early cancer development and later progression is lagging behind due to the difficulty of analysing and following early tissue changes in the surrounding of cancer cells in vivo. In our research proposal we will use a combination of original tools developed in the lab and state of the art technologies to overcome some of these constraints and expand our understanding of which cells in the niche support early cancer cell growth. We also aim to reveal their mechanism of action and identify approaches to block the niche supportive activity. Our five-year plan has three main objectives (I, II, III), which we will meet using two original strategies. With the first strategy we will visualize the early tumourigenic niche in vivo. This will allow us (I) to identify and characterize novel cellular components during dynamic niche evolution both in the context of metastatic colonization as well as during primary tumour onset. We will also use this original approach (II) to deepen our understanding of neutrophils in cancer, a particularly crucial emerging component of the cancer niche, whose role is still debated. After dissemination, cancer cells may encounter an unfavourable niche, failing to start colonization and remaining dormant within the tissue. However, the quiescent-permissive tissue can change, cancer cells reactivate and form metastases even a long period after tumour resection. Little is known about the changes in the niche of dormant cells capable of triggering their reactivation. With the second strategy we will generate an in vivo a controllable, dormant-permissive tissue (III) to screen for potential signals triggering dormant cells reactivation. Fields of science medical and health sciencesclinical medicineoncology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-COG - ERC Consolidator Grant Call for proposal ERC-2016-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator THE FRANCIS CRICK INSTITUTE LIMITED Net EU contribution € 2 000 000,00 Address 1 midland road NW1 1AT London United Kingdom See on map Region London Inner London — West Camden and City of London Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE FRANCIS CRICK INSTITUTE LIMITED United Kingdom Net EU contribution € 2 000 000,00 Address 1 midland road NW1 1AT London See on map Region London Inner London — West Camden and City of London Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00