NO donor-based therapy has been advanced from an NO donor alone towards the (1) co-administration of NO donors with other chemo-/radio-/immune-therapy; (2) hybridization of NO donors with gaseous transmitters, such as hydrogen sulfide (H2S) and carbon monoxide (CO); (3) combinational use of iNOS and COX inhibitors; and (4) application of drug delivery systems, such as nanotechnology, to deliver a high level of NO to the tumor sites. Here, NOS2 is linked to neoplasm.