Obiettivo Oncogenic signalling networks display a remarkable degree of plasticity. Despite only a limited number of alterations in oncogenes and tumour suppressor genes in most tumours, the majority of targeted therapeutics (monoclonal antibodies and small-molecule kinase inhibitors) does not strongly improve the survival of cancer patients and suffers from the rapid development of resistance. The rising number of targeted drugs in clinical use inhibits only a very limited number of protein targets (largely kinases). Consequently, most intracellular non-kinase oncoproteins remain untargeted. We have previously established the use of small engineered antibody mimics, termed monobodies, to potently and specifically target intracellular protein-protein interactions mediated by the SH2 domains of oncogenic kinases and phosphatases. Expression of SH2-targeting monobodies resulted in the inhibition of signalling and oncogenesis of these oncoproteins. Here, we aim at developing monobody binders to 10 key intracellular oncoproteins for which no chemical inhibitors exist and testing their activity in cancer cells. To enable a possible clinical translation of monobody-based therapeutics, we will develop methods to deliver monobody proteins into cells, including cell-penetrating peptides, bacterial toxins and biocompatible nanocarriers. 'Mirror-image' monobodies, composed of D-amino acids, will be developed and tested to increase intracellular and plasma stability and to limit immunogenicity. The developed monobodies and delivery systems are planned to be tested in mouse cancer models. Our goal is to establish monobodies as novel class of intracellular protein-based therapeutics. We hope to kick off their use beyond basic research tools towards possible applications in cancer patients. This innovative endeavour uses state-of-the-art protein engineering techniques to address a central problem in cancer medicine and may provide a ground-breaking new approach to target cancer. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineoncology Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-CoG-2015 - ERC Consolidator Grant Invito a presentare proposte ERC-2015-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante PHILIPPS UNIVERSITAET MARBURG Contribution nette de l'UE € 1 419 148,41 Indirizzo BIEGENSTRASSE 10 35037 Marburg Germania Mostra sulla mappa Regione Hessen Gießen Marburg-Biedenkopf 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 € 1 419 148,41 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto PHILIPPS UNIVERSITAET MARBURG Germania Contribution nette de l'UE € 1 419 148,41 Indirizzo BIEGENSTRASSE 10 35037 Marburg Mostra sulla mappa Regione Hessen Gießen Marburg-Biedenkopf 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 € 1 419 148,41 ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Partecipazione conclusa Svizzera Contribution nette de l'UE € 576 906,59 Indirizzo BATIMENT CE 3316 STATION 1 1015 Lausanne Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Région lémanique Vaud 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 € 576 906,59