The ColoForetell project has identified as a primary goal, the discovery & verification of predictive pharmaco'omic biomarkers & imaging methods for REG response in mCRC patients who have disease progression despite all currently available standard therapies.

Within this context Three Key Objectives & Six Associated Milestones have been identified:

Objective 1: Interrogate the effect of REG in a cohort (n=70) of characterized metastatic CRC PDX models

Demonstration of an mCRC Xenopatient platform as a reliable clinical surrogate tool for identifying REG response biomarkers

Elucidation of longitudinal effects of REG treatment on tumour blood vessels & description of the relationship between xenopatient response phenotype and pharmacodynamic / tumor response phenotype. 

Objective 2: Apply an integrated whole exome sequencing (WES) / Reverse Phase Protein Array (RPPA) approach to identify putative biomarkers & interrogate cellular signaling pathways in mCRC PDX models following REG treatment: Derive population-based associations between defined genetic lesions/phophoprotein activities and response to REG

Validated set of predictive exon mutations in REG-treated mCRC Xenopatients. Somatic mutations in all known expressed genes (the "exome") will be assessed and verified to determine the relationship between the presence of specific mutations and outcome following REG therapy in mCRC xenopatients

Completion of Integrated analyses of 'omic BM candidates using conventional statistics and Systems Modeling

Objective 3: Assess DCE-MRI as an Imaging Biomarker of response for REG implementing 'next-generation' orthoxenograft mCRC PDX models

Establish orthotopic mCRC PDX models for REG response phenotypes 

Demonstration of the predictive power of DCE-MRI as a REG imaging biomarker of response