دانلود رایگان مقاله متابولیسم اسید آمینه غیرضروری در سرطان سینه

abstract

Interest in studying cancer metabolism has risen in recent years, as it has become evident that the relationship between cancer and metabolic pathways could reveal novel biomarkers and therapeutic targets. Metabolic starvation therapy is particularly promising due to its low toxicity. Nonessential amino acids are promising metabolites for such therapy because they become essential in many tumor cells, including breast cancer cells. This review will focus on four nonessential amino acid metabolism pathways: glutamine eglutamate, serineeglycine, cysteine, and arginineeproline metabolism. Recent studies of these amino acids have revealed metabolic enzymes that have the potential to be effective as cancer therapy targets or biomarkers for response to metabolic starvation therapy. The review will also discuss features of nonessential amino acid metabolism that merit further investigation to determine their relevancy to breast cancer treatment.

6. Concluding remarks

Targeting nonessential amino acid metabolism is an emerging field for cancer therapy, especially in breast cancer, as it shows promise to selectively target aspects of tumor metabolism with minimal toxic side effects. Various metabolites and metabolic enzymes have merit as biomarkers and therapy targets for monotherapies or combination therapies. Moreover, amino acid metabolite levels in plasma have potential as accessible biomarkers for determining treatment regimens, and to follow during treatment to determine outcome and therapy response. The expression levels of proteins that modulate amino acid metabolism may also be useful biomarkers for selecting appropriate metabolic therapies for precision-guided medicine. It is also worth noting that while glutamine and serine metabolism have been well studied in the context of breast cancer, the metabolism of other nonessential amino acids is a more nascent field. In a recent study that profiled metabolites in breast tumors, alanine was the most significantly altered metabolite, with especially high levels in ER-negative breast cancers and a two-fold increase in tumor over normal. This most closely correlated with downregulation of 4-aminobutyrate aminotransferase (ABAT), which converts alanine to malonate semialdehyde to feed the TCA cycle. Low ABAT expression is associated with poor prognosis, so high levels of alanine may contribute to aggressive breast cancer (Budczies et al., 2013). This illustrates the need for significant future work to determine the merit of targeting alanine metabolism for breast cancer therapy, and also indicates that potential new clinical targets can be identified through investigating metabolic pathways in cancer.