High levels of serum cholesterol increase the risk of developing vessel co‐opting tumors in colorectal cancer liver metastases

Cholesterol availability has been implicated in cancer progression. Here, we demonstrate the connection between blood cholesterol concentration, the development of distinct histopathological growth patterns (HGPs) in colorectal cancer liver metastases (CRCLM), and new avenues of treatment for patients. Our study reveals that serum cholesterol levels correlate with the different HGPs, and patients on statins had desmoplastic HGPs and improved overall survival. We also demonstrate, in an in vivo mouse model, that inhibition of key modulators of cholesterol metabolism, using antiproprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, attenuated the development of CRCLM tumors, as well as the formation of vessel co-opting lesions. Our findings underscore the importance of cholesterol in CRCLM and the potential clinical application of evolocumab to mitigate the growth of these histological types of tumors in CRCLM.