ABSTRACT
Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed.
ABSTRACT
There have been significant advances over the last decade in the understanding of cellular, biochemical, and molecular effects of ionizing radiation combined with certain types of cytotoxic drugs and prodrugs, as well as new "targeted" biological agents in human tumor and normal cells. At the same time, new information has evolved regarding specific genetic and epigenetic changes found in certain human cancers, which result in alterations in ionizing radiation damage recognition and damage repair processes. As a result, novel targeting approaches for human tumor radiosensitization is an active area for translational and clinical research in radiation oncology. In this article, we review the current status of existing and new radiosensitizing regimens.
