The aim of the On-treatment biomarkers in metastatic ColorectAL cancer for Life (On-CALL) study is to generate further knowledge on the evolutionary progression of mCRC during treatment with curative intent, and to elucidate the mechanisms underlying the therapeutic failure still seen in a substantial number of patients.
The specific objectives are:
* To comprehensively characterise the spatial intertumoural, intermetastatic and intrametastatic genetic heterogeneity
* To delineate differences in the prevalence and type of genetic heterogeneity, as well as tumour evolvability, according to metastatic site
* To examine the associations between spatial and temporal heterogeneity
* To examine ctDNA quantity and quality as an early biomarker for response to neoadjuvant treatment
* To examine ctDNA quantity and quality as an early biomarker for response to adjuvant treatment
* To evaluate the relationship between phylogenetic patterns, i.e. the tumour evolvability, and survival in relation to different treatment modalities
* To examine the heterogeneity of the tumour microenvironment in relation to the genetic heterogeneity and evolvability of the tumours
* To examine circulating immune cells and inflammatory biomarkers, and their relationship with the genetic and microenvironmental heterogeneity of the tumours
* To delineate parallel events at the transcriptomic and proteomic levels, with particular reference to their potential utility as clinically relevant surrogate biomarkers of genetic alterations underlying the evolvability of the tumours
