Objective The transcription factor Myc plays a central role in tumourigenesis but was deemed undruggable due to it being an essential protein. However, recent proof-of-principle studies in mice using a dominant negative allele of Myc demonstrated the dependency of established tumours on Myc function and showed that mice tolerated Myc inhibition to a degree that allowed tumour regression. In line with these observations my group found Myc to regulate distinct sets of genes at low, physiological and high, oncogenic levels, because promoters differ in their affinity for Myc. This notion implies the compelling possibility to specifically target the oncogenic functions of Myc.TarMyc aims to address four key questions required to bring this new concept from bench to bedside. Firstly, TarMyc will estimate the therapeutic window of Myc inhibition in vivo by expressing shRNAs against Myc in mice with established solid tumours. Secondly, TarMyc aims to identify in vivo Myc target genes crucial for tumourigenesis. Thirdly, this proposal aims to elucidate the role of Myc’s differential promoter affinity in untransformed cells. Analysis of published gene expression datasets revealed Myc binding to low-affinity promoters during the process of tissue regeneration. Thus, by characterizing the regeneration programme induced by Myc we hope to gain further insight on the therapeutic window of Myc inhibition and assess potential side-effects in a Myc-targeting anticancer therapy. Fourthly, we aim to develop strategies to interfere with the oncogenic functions of Myc by (i) developing a novel class of drugs that reduce Myc’s cellular concentrations, and (ii) by testing the therapeutic potential of Myc target genes by inhibiting their function in tumour models.Taken together, TarMyc takes on the challenge of inhibiting the oncogenic functions of Myc in a highly multidisciplinary approach using state-of-the-art molecular biology, advanced tumour models and new concepts in drug development. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesmolecular biology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-STG - ERC Starting Grant Call for proposal ERC-2017-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Net EU contribution € 1 497 905,00 Address Sanderring 2 97070 Wuerzburg Germany See on map Region Bayern Unterfranken Würzburg, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments 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 JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Germany Net EU contribution € 1 497 905,00 Address Sanderring 2 97070 Wuerzburg See on map Region Bayern Unterfranken Würzburg, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments 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
