Redox Metabolism: a Double Edge Sword Sustaining the Adaptive Resistance to Therapy in Cancer

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About this Research Topic

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Background

Cancer cell metabolic reprograming contributes to the production of Reactive Oxygen Species (ROS) which, at moderate levels, can act as second messengers modulating several redox-signaling pathways essential for cell survival and proliferation. However, when not properly balanced ROS overproduction can induce cell death. Consequently, cancer cells are often characterized by an up-regulation of antioxidant systems, as proven by the evidence that pro-oxidant therapies are often ineffective. Interestingly, it has been reported that therapy-induced stress conditions stimulate a metabolic shift from aerobic glycolysis to mitochondrial oxidative phosphorylation (OXPHOS), able to guarantee rapid ATP generation as well as biosynthesis of nucleotides, proteins and lipids to support tumor growth. A growing body of evidence in different cancer types, indicates that cancer stem cells (CSCs), a limited cell population into a tumor bulk, are characterized by oxidative metabolism, high antioxidant defenses and, consequently are critically implicated in therapy-response.


Therapy-induced stress conditions can lead to the activation of redox signaling pathways and the maintenance of an efficient oxidative metabolism allowing cancer cell survival. In addition, taken into consideration that CSCs are critically involved in tumor growth and repopulation, a critical appraisal of their metabolism needs to be focused in this Research Topic. The emerging knowledge that CSCs acquire both a proliferative, epithelial-like (E) and quiescent, mesenchymal-like (M) states and that the equilibrium of these dynamic states depends on tumor microenvironment and alterations of redox states suggests that CSC plasticity may contribute to therapeutic resistance. Therefore, it is imperative to characterize metabolic reprogramming and its relationships with redox-signaling network in order to identify potential specific markers and targets for enhancing therapy efficacy.


The scope of the Research Topic is to shed light on redox metabolism in cancer in order to identify specific lineages and state redox vulnerabilities that can be targeted for counteracting therapy tolerance and improving treatment efficacy both from a basic and clinical research point of view. We welcome the submission of Original Research, Review, mini-Review and Perspective articles, covering, but not limited to, the following subtopics:

- Redox signaling pathways and cancer cell response

- Metabolic reprogramming in cancer and therapy resistance

- Antioxidants and adaptive resistance of cancer to therapies

- Manipulation of redox metabolism and effects on therapy response

- Tumor microenvironment and therapy response

- Cancer stem cell plasticity and treatment failure

- Epigenetic mechanisms underlying therapy tolerance

- Design and discovery of new specific targeted redox active molecules

Keywords: redox signaling, antioxidants, chemoresistance, radioresistance, therapy tolerance, microenvironment, cancer stem cells, Epithelial-Mesenchimal transition, Metabolic reprogramming

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