Membrane Redox Potentials as Determinants of Cancer Cell Survival and Therapy Resistance

Membrane redox potentials represent a critical yet underexplored dimension of cancer biology. These potentials, generated across mitochondrial and plasma membranes through electron transport and redox-active enzymes, tightly regulate bioenergetics, reactive oxygen species (ROS) signaling, and cell fate. In cancer, aberrant shifts in membrane redox states foster metabolic reprogramming, adaptation to oxidative stress, and evasion of apoptosis, ultimately conferring a survival advantage under hostile microenvironmental conditions. Moreover, altered redox potentials modulate ion channels, transporter activity, and redox-sensitive signaling pathways, contributing directly to resistance against chemotherapy, radiotherapy, and targeted therapies. This review integrates current knowledge on the role of membrane redox potentials in cancer cell survival and therapeutic resistance, emphasizing the interplay between redox biology, tumor heterogeneity, and treatment outcomes. We highlight advances in methodologies to measure membrane redox states, discuss novel small molecules and nanotechnology-based interventions aimed at redox modulation, and propose future directions for exploiting membrane redox vulnerabilities as precision oncology strategies. Keywords: Membrane redox potential, Cancer metabolism, Therapy resistance, Reactive oxygen species (ROS), Mitochondrial dysfunction