Objectif Melanoma (cancer of the melanocyte) kills over 20,000 Europeans each year and incidence continues to rise rapidly. BRAF(V600E) inhibitors have led to clinically significant improvements in outcomes for melanoma patients, yet many patients with metastatic melanoma rapidly succumb to the disease due to eventual chemoresistance, or insensitivity to the drug. Thus, it is critical to identify new therapies that can act alone, or be combined with available treatments for enhanced efficacy and/or to overcome drug resistance. An important and new therapeutic concept for melanoma is to target the melanocyte lineage. Recent evidence reveals that a melanocyte lineage specific programme maintains melanoma survival, and we have engineered the first animal model in zebrafish to demonstrate that targeting the master melanocyte lineage transcription factor MITF leads to rapid melanoma regression. Thus, understanding and targeting the melanocyte lineage is directly relevant to melanoma, and reveals therapeutically targetable processes.Our vision is to use live-imaging of the melanocyte lineage as the basis for phenotypic chemical screens in zebrafish to find drugs/leads and identify targetable processes that might elucidate pathways for cancer therapy. Screening for targets of the melanocyte lineage is highly relevant to melanoma because melanocytes are the melanoma cell of origin, and genes that specify the melanocyte stem cells and the lineage during embryogenesis are the same genes that play fundamental roles in cancer. We will use innovative chemical-biology to capture and validate targets in vivo, and perform chemo-preventative and -therapeutic trials in zebrafish melanoma models using known and novel drug-delivery methods. Ultimately, we aim to translate our most promising drug/leads and targets into the mammalian system, to establish the basis for patent applications and clinical trials. Champ scientifique medical and health sciencesclinical medicineoncologyskin cancermelanomanatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineembryology Mots‑clés Melanocyte Melanoma Cancer Stem Cells Drug-lead Drug-Development Target ID Small molecules Biochemistry Imaging Tumour Regression Genetic Engineering CRISPR Zebrafish Model Systems Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-CoG-2014 - ERC Consolidator Grant Appel à propositions ERC-2014-CoG Voir d’autres projets de cet appel Régime de financement ERC-COG - Consolidator Grant Institution d’accueil THE UNIVERSITY OF EDINBURGH Contribution nette de l'UE € 1 865 345,00 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Royaume-Uni Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 865 345,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire THE UNIVERSITY OF EDINBURGH Royaume-Uni Contribution nette de l'UE € 1 865 345,00 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 865 345,00