The Role of One-Carbon Metabolism in Cancer Progression, Therapy, and Resistance

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Background

Metabolic reprogramming is a well-known feature of cancer, which promotes cancer initiation and progression. Highly activated one-carbon metabolism can create an upregulated metabolic network in tumors with high clinical relevance and can also meet the unique requirement of high metabolic flux, which provides a large number of macromolecular precursors. One-carbon metabolism includes folate cycle, methionine cycle and transsulfuration pathway, which is involved in supporting the survival and rapid and unregulated proliferation of cancer cells, including nucleotide synthesis, the epigenetic signature (DNA methylation, histone methylation) and redox defense. Furthermore, one-carbon metabolism is considered a new metabolic vulnerability that increases the specificity and sensitivity of existing cancer therapies and overcomes tumor resistance. With the further exploration of metabolic reprogramming of one-carbon metabolism in cancer cells, a variety of anti-tumor therapies have been proposed, including dietary interventions, inhibiting key metabolic enzymes of one-carbon metabolism, and modifying the epigenetic signature (DNA methylation, histone methylation).

One-carbon metabolism is involved not only in nucleotide, protein, and lipid biosynthesis, but also in DNA methylation, histone methylation and redox homeostasis. The expanding understanding of one-carbon metabolism may facilitate the development of targeted anti-metabolite therapies by highlighting new translational opportunities for dietary interventions, drug development and drug resistance overcoming. Understanding these roles could create new therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism. This Research Topic welcomes Original Research, Mini Review, Clinical Trial, and Perspective articles covering, but not limited to, the following sub-topics:

• Studies that identify or expand knowledge of the mechanisms of dietary interventions affecting cancer outcomes through controlled and reproducible changes to one-carbon metabolism.
• Studies that target metabolic enzymes in serine, glycine and one-carbon metabolism for cancer diagnosis, therapeutic approaches, or tumor resistance.
• Identification or assessment of biomarkers related to one-carbon metabolism in cancers
• Metabolic reprogramming and tumor resistance
• Studies that describe the mechanisms of regulating redox homeostasis of the tumor microenvironment in one-carbon Metabolism
• Studies identifying the mechanisms of cancer epigenetic alterations in conjunction with one-carbon metabolism

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: One-carbon metabolism, Therapy resistance, Dietary interventions, Redox homeostasis, Epigenetic alterations

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