Targeting IL-11 signaling in colon cancer

The development of Colorectal cancer (CRC), the fourth most common cause of malignancy worldwide, is driven by the sequential accumulation of genetic changes. In the Western world, more than 80 % of sporadic CRC cases arise from aberrant activation of the WNT-pathway, including mutations in the adenomatous polyposis coli (APC) tumor suppressor gene and CTNNB1 transcription factor, and followed by mutations in K-RAS, PIK3CA, SMAD4 and TP53 as the tumor emerges and progresses [1] (Fig 1, top). Recent evidence suggests that these tumor intrinsic events are accompanied by ‘inflammatory gene signatures ’ [2], which were originally identified in colitis-associated cancer (CAC) and have long been suspected to account for the increased CRC lifetime risk in patients suffering from ulcerative colitis (UC). Inflammation associated with UC is characterized by myeloid cells and T-helper interleukin (IL)-