Over the last decade, three major advances have contributed in improving the response rates against
cancer including,
immunotherapy; greater understanding of the molecular, biochemical, and cellular mechanisms in
carcinogenesis thereby providing drug targets; and identification of reliable
biomarkers for early detection to facilitate the earlier stage treatment of disease. However, no single universal
cancer cure has yet been found, although combinations from the above areas have steadily improved survival outcomes. Hence,
chemotherapy remains a key component in the oncologist's arsenal for
cancer therapy, despite frequent development of drug resistance and more aggressive
cancers with onset of advanced stage
metastases. The focus here is to explore the repurposing of old drugs that cause pro-oxidative overload to overcome onset of resistance to
chemotherapy and enhance chemotherapeutic responses, particularly against metastatic
cancer. Excellent examples of US Food and Drug Administration approved drugs suitable for repurposing are the potent and specific thioreductase inhibitor
auranofin and the nonsteroidal anti-inflammatory drug,
celecoxib. Recently, both drugs were shown to selectively target and kill metastatic
cancer cells and cancer stem cells (CSCs), predominantly by promoting excessive mitochondrial
reactive oxygen species. Thus, targeting intracellular redox systems of advanced stage metastatic
cancer cells and CSCs can promote an overload of pro-oxidative stress to activate the intrinsic pathway for programmed cell death. It is envisaged that more clinical studies will incorporate longer term use of repurposed drugs, such as
auranofin or
celecoxib, to target redox systems in
cancer cells as part of common practice postcancer diagnosis, providing enhanced chemotherapeutic responses and increased
cancer survival.