Cel Monoclonal antibodies against the EGF receptor (EGFR) provide substantive benefit to colorectal cancer (CRC) patients. However, no genetic lesions that robustly predict ‘addiction’ to the EGFR pathway have been yet identified. Further, even in tumours that regress after EGFR blockade, subsets of drug-tolerant cells often linger and foster ‘minimal residual disease’ (MRD), which portends tumour relapse. Our preliminary evidence suggests that reliance on EGFR activity, as opposed to MRD persistence, could be assisted by genetically-based variations in transcription factor partnerships and activities, gene expression outputs, and biological fates controlled by the WNT/beta-catenin pathway. On such premises, BEAT (Beta-catenin and EGFR Abrogation Therapy) will elucidate the mechanisms of EGFR dependency, and escape from it, with the goal to identify biomarkers for more efficient clinical management of CRC and develop new therapies for MRD eradication. A multidisciplinary approach will be pursued spanning from integrative gene regulation analyses to functional genomics in vitro, pharmacological experiments in vivo, and clinical investigation, to address whether: (i) specific genetic alterations of the WNT pathway affect anti-EGFR sensitivity; (ii) combined neutralisation of EGFR and WNT signals fuels MRD deterioration; (iii) data from analysis of this synergy can lead to the discovery of clinically meaningful biomarkers with predictive and prognostic significance.This proposal capitalises on a unique proprietary platform for high-content studies based on a large biobank of viable CRC samples, which ensures strong analytical power and unprecedented biological flexibility. By providing fresh insight into the mechanisms whereby WNT/beta-catenin signalling differentially sustains EGFR dependency or drug tolerance, the project is expected to put forward an innovative reinterpretation of CRC molecular bases and advance the rational application of more effective therapies. Dziedzina nauki natural sciencesbiological sciencesgeneticsmedical and health sciencesclinical medicineoncologycolorectal cancerengineering and technologyenvironmental engineeringenergy and fuels Słowa kluczowe Colorectal Cancer Targeted therapy Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-2016-COG - ERC Consolidator Grant Zaproszenie do składania wniosków ERC-2016-COG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-COG - Consolidator Grant Instytucja przyjmująca UNIVERSITA DEGLI STUDI DI TORINO Wkład UE netto € 1 793 421,00 Adres VIA GIUSEPPE VERDI 8 10124 Torino Włochy Zobacz na mapie Region Nord-Ovest Piemonte Torino Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 793 421,00 Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko UNIVERSITA DEGLI STUDI DI TORINO Włochy Wkład UE netto € 1 793 421,00 Adres VIA GIUSEPPE VERDI 8 10124 Torino Zobacz na mapie Region Nord-Ovest Piemonte Torino Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 793 421,00
