In this respect, IL-6 trans-signaling via sIL-6R has recently emerged as a central driver of Kras mutant LAC and CRC, the latter via EGFR signaling which paves the way to potentially exploit components of the IL-6 trans-signaling axis (including ADAM17) as therapeutic targets in patients who develop resistance to EGFR blockade [29,97,132,197]. This evidence concerns the gene IL6R and colorectal carcinoma.