KRAS and colorectal carcinoma: For instance, in CRC, the expansion of KRAS G12D mutant subclones is not only directly related to resistance to anti-EGFR therapy, but its epigenetic features (such as the opening of AP-1 transcription factor binding sites) can also induce a pro-metastatic phenotype in stromal cells by activating IL-11 paracrine signaling (105).