Studies in murine models of lymphoma, fibrosarcoma, and melanoma have shown that the dose–response curve of systemically administered NGR-TNF is markedly different from that of TNF: while both TNF and NGR-TNF have therapeutic anti-cancer activity at doses in the microgram range, only NGR-TNF can induce anti-tumor responses when administered at doses in the picogram range (e.g., 100 pg/mouse). This evidence concerns the gene RTN4R and cancer.