The central aim is to develop in silico therapy response predictors that allow individualised treatment based on patient-specific driver and resistance mechanisms, thus significantly increasing response and cure rates in Colon Cancer (CC).
To achieve this central aim, the specific objectives of COLOSYS are:
- Identify known and novel CC driver genes by integration of multiple data types from public tumour data repositories;
- Build CC-specific regulatory maps centred around the driver genes and use these to generate logic multi-scale models of mechanisms controlling cellular viability;
- Identify treatments that diminish cell viability and test these in large panels of established cell lines and patient organoid cultures;
- Identify cases of unexpected intrinsic resistance, construct in vitro models of acquired resistance, perform perturbation experiments and model these resistance mechanisms in silico;
- Identify, based on the in silico resistance models, new targets leading to novel combination treatments that overcome resistance;
- Validate these treatment strategies pre-clinically in patient-derived xenograft (PDX) models, organoid trials and in samples from patients included in clinical trials.