Targeting Redox Metabolism For Cancer Therapy: From The Bench To The Bedside

Abstract

Relative to normal cells, cancer cells have been shown to demonstrate fundamental differences in oxidative metabolism leading to increased steady-state levels of superoxide and hydrogen peroxide. Alterations in cancer cell oxidative metabolism in turn lead to disruptions in many redox sensitive signaling and gene expression pathways that impact cell growth, differentiation, genomic instability, and cancer progression. Cancer cells adapt to this altered metabolic state by activating many signaling and gene expression pathways that allow them to survive and continue to progress to malignancy, but preclude normal cellular differentiated function. The Free Radical Theory of Cancer originally proposed in the late 1970’s predicted that this fundamental defect in cancer cell oxidative metabolism would represent an “Achilles heel” that could be exploited for cancer therapy. Implementation of this approach clinically has required a significant body of basic science work to clarify the redox biochemistry defining these metabolic frailties and compounds that can be utilized to target these processes. The current lecture will address several basic science and clinical approaches to targeting oxidative metabolism for the purpose of improving cancer therapy.