Obiettivo 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. Campo scientifico 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 Parole chiave Melanocyte Melanoma Cancer Stem Cells Drug-lead Drug-Development Target ID Small molecules Biochemistry Imaging Tumour Regression Genetic Engineering CRISPR Zebrafish Model Systems Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-CoG-2014 - ERC Consolidator Grant Invito a presentare proposte ERC-2014-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante THE UNIVERSITY OF EDINBURGH Contribution nette de l'UE € 1 865 345,00 Indirizzo OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Regno Unito Mostra sulla mappa Regione Scotland Eastern Scotland Edinburgh Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 865 345,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto THE UNIVERSITY OF EDINBURGH Regno Unito Contribution nette de l'UE € 1 865 345,00 Indirizzo OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Mostra sulla mappa Regione Scotland Eastern Scotland Edinburgh Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 865 345,00