Murine colorectal cancer model captures common mutations and immune-excluded features

Preclinical colorectal cancer studies can be limited by models that do not represent clinically relevant tumor subtypes. In a study published in *BMC Medicine*, investigators developed KAP cells from mouse colorectal organoids carrying Kras G12D and Trp53 deletion, then used CRISPR-Cas9 to knock out Apc. The cells were implanted orthotopically in syngeneic B6 mice to generate rectal tumors. The study also assessed tumor features and responses to FOLFOX chemotherapy and radiation; the supplied report does not give animal numbers or numerical response results.

KAP tumors were highly aggressive and invasive. They showed poorly differentiated gland-like structures, dense collagen deposition, immature vasculature and few intratumoral immune cells—features the authors say resemble immune-excluded human colorectal cancer. After treatment with FOLFOX and radiation, outcomes in the mice were reported to be similar to those seen in patients, although specific measures are not provided in the supplied text.

The model may support preclinical research into tumor biology and treatment response in low-infiltration colorectal cancer. It is an animal model, however, and similarity to patient outcomes does not establish that findings will translate to clinical benefit. The work was supported by University of Rochester and NIH funding; the authors reported no competing interests.