Using mouse <i>Apc</i> / <i>Kras</i> / <i>Trp53</i> ( <i>AKP</i> ) colorectal cancer organoids, we found that macrophages and/or macrophage-conditioned medium reduced sensitivity to the MEK inhibitor trametinib and the pan-RAS inhibitor RMC-6236. This evidence concerns the gene APC and colorectal cancer.