Redox Regulation of Cancer Metabolism

Dear Colleagues,

Metabolic rewiring represents a fundamental hallmark of cancer, enabling malignant cells to sustain uncontrolled proliferation, enhance survival and differentiation, and adapt to adverse microenvironmental conditions. Accumulating evidence indicates that redox homeostasis plays a pivotal role in orchestrating these metabolic adaptations. Metabolic reprogramming profoundly influences the cellular redox equilibrium, thereby modulating tumor progression, metastatic dissemination, and therapeutic responsiveness.

Reactive Oxygen Species (ROS), whose intracellular concentrations are normally tightly controlled by redox regulatory systems, can act as potent pro-growth mediators that promote tumor initiation, progression, angiogenesis, and metastasis. Paradoxically, excessive ROS generation is also a key mechanism underlying the cytotoxic effects of many chemotherapeutic agents and radiotherapy. Consequently, cancer cells exhibit an increased dependence on antioxidant defense mechanisms compared with their normal counterparts. These include the pentose phosphate pathway-derived Nicotinamide Adenine Dinucleotide Phosphate (NADPH), glutathione (GSH), thioredoxin (TXN), and a broad spectrum of antioxidant enzymes—such as mitochondrial and cytosolic peroxiredoxins (PRXs), glutathione peroxidases (GPXs), catalase, and superoxide dismutases (SODs)—as well as their principal transcriptional regulator, Nuclear Factor Erythroid 2-Related Factor 2 (NRF2).

Given that mitochondria constitute a major source of ROS, the targeted modulation of mitochondrial function has emerged as a promising therapeutic approach to induce cancer-selective cell death through redox perturbation. Elucidating the intricate crosstalk between redox signaling and cancer metabolism is therefore essential for identifying novel metabolic vulnerabilities and redox-sensitive therapeutic targets.

This Special Issue invites original research and comprehensive review articles that examine how redox regulation shapes cancer metabolic pathways. Particular emphasis is placed on the roles of redox-dependent enzymes and transcription factors (e.g., NRF2, HIF-1α, AMPK, p53), as well as on antioxidant and redox-modulating strategies in cancer therapy. Contributions addressing mechanistic insights, biomarker identification, and translational applications are especially encouraged.

Sincerely,

Prof. Dr. Marta Menegazzi
Dr. Adriana Celesia
Guest Editors

Dr. Alessia Cardile
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• redox homeostasis
• cancer metabolism
• reactive oxygen species (ROS)
• metabolic reprogramming
• oxidative stress
• Nrf2
• HIF-1α
• mitochondrial metabolism
• antioxidant therapy
• metabolic vulnerabilities