D-Amino Acids and Cancer: Friends or Foes?

α-amino acids exist in two configurations, named D-(dextro) and L-(levo) enantiomers. L-amino acids are used in protein synthesis and play a central role in cell metabolism. The effects of the L-amino acid composition of foods and the dietary modifications of this composition on the efficacy of cancer therapies have been widely investigated in relation to the growth and reproduction of cancerous cells. However, less is known about the involvement of D-amino acids. In recent decades, D-amino acids have been identified as natural biomolecules that play interesting and specific roles as common components of the human diet. Here, we focus on recent investigations showing altered D-amino acid levels in specific cancer types and on the various roles proposed for these biomolecules related to cancer cell proliferation, cell protection during therapy, and as putative, innovative biomarkers. Notwithstanding recent progress, the relationship between the presence of D-amino acids, their nutritional value, and cancer cell proliferation and survival represents an underrated scientific issue. Few studies on human samples have been reported to date, suggesting a need for routine analysis of D-amino acid content and an evaluation of the enzymes involved in regulating their levels in clinical samples in the near future.