Our data suggest that chemo- and immuno-resistance to anthracyclines are associated in colon cancer cells and rely on a common mechanism, that is the inability of doxorubicin to induce iNOS. Therefore NO donors might represent a promising strategy to restore both chemosensitivity and immunosensitivity to doxorubicin in resistant cells. This evidence concerns the gene NOS2 and malignant colon neoplasm.