Nitric Oxide Based Therapeutics for the Treatment of Lung Cancer

Nitric oxide (NO) has a broad spectrum of actions in physiological and pathological processes.  NO-donor drugs have shown therapeutic effect in several cancer types by inducing apoptosis but the concentrations required have suggested limited clinical applicability.  For cancers such as non-small cell lung cancer where most therapies are not curative, there remains a need for effective treatments. 

Scientists at the National Cancer Institute have identified a diazeniumdiolate-based NO releasing prodrug, JS-36-25, with selective cytotoxicity towards cancer cells.  This prodrug has potent tumoristatic activity in lung cancer cells in vitro and in mice xenografts.  Treatment with JS-36-25 in vivo led to 85% reduction of tumor growth.  The tumoristatic potency of the compound had a negative correlation with the level of endogenous reactive oxygen species (ROS) in the cancer cells.  Thus, in addition to potent tumoristatic activity when administered alone, this compound is predicted to have a strong synergy with therapeutics that act through generation of ROS, such as bortezomib, doxorubicin, as well as high-energy radiation.