From the data emerging in this review, patients with chemoresistant CRCs cannot be retrained only through the presence or absence of K-ras mutation, evaluated by i.e., cfDNA analysis [100, 101], but it is necessary, through the analysis of markers such as RAGE or PDL-1 expression, through immunocytochemical approach [102–104] on i.e., circulating tumour cells [105–107], to verify how to support the possible choice of a targeted therapy or in the absence of this, to identify an optional and personalized therapeutic intervention (Figure 3). Here, AGER is linked to neoplasm.