Besides, in our opinion, the finding that RIZ2 overexpression triggers the increase of EGF secretion in the setting of CMS1 background, such as in DLD1 cells, could represent a new element in the effort to better characterize the CRC molecular subtypes and to understand the players able to modify the tumor microenvironment, the immune-escape and, in turn, the optimized sensitivity to first and second line treatments [33, 42]. Here, EGF is linked to neoplasm.