ALFAOMEGA Master Observational Trial

AlfaOmega is an observational study that will follow a stage-mixed cohort of at least 500 patients through their course of treatments, until death or a minimum of 5 years. Patients will be longitudinally sampled and matched clinical data (including imaging) will be collected. Via a multi-tiered informed consensus process, AlphaOmega will also allow to develop companion diagnostics for molecular enrichment strategies in AIRC-driven proof-of-concept trials. To achieve the required level of 'experimental precision', patients will enter AlphaOmega at two different 'therapeutic checkpoints': i) prior to a surgical event or ii) prior to a systemic treatment. In the latter case patients with no previous lines of therapy for metastatic disease will be privileged. To optimize the enrollment of patients, the longitudinal collection of data/samples and their logistic management, AlphaOmega has been designed as a flexible infrastructure organized in TIERS for the stepwise comprehension of the biological processes that drive tumor evolution, and precisely: * TIER1, Monitoring: the ability to follow CRC evolution under standard of care treatments and to define new evolution-linked biomarkers. This will be achieved through the collection of clinical data, imaging data, FFPE tissue and frozen plasma/PBMC. * TIER2, Modelling: the ability to develop pertinent experimental models to study evolutionary mechanisms and define evolution-targeting therapeutic strategies. This will be achieved through the collection of Fresh Tissue, Whole Blood, Stools, Buccal Swabs and other fluids. * TIER3, Linking: the ability to access data and samples of patients enrolled in proof-of-concept trials to prove the efficacy and study/understand resistance mechanisms of evolution-targeting therapies. This will be achieved by introducing the connection in the trial protocol.