From Fly to Human: Translational Relevance of Drosophila Models in the Study of Vitamin B6 and Cancer Relationship

Vitamin B6 is an essential micronutrient whose biologically active form, pyridoxal 5′-phosphate (PLP), acts as a cofactor in metabolic reactions linked to tumorigenesis and also functions as an antioxidant. Low plasma PLP levels are consistently associated with cancer, but studies on dietary intake have yielded conflicting results. Overall, evidence suggests that the effects of vitamin B6 deficiency on cancer are context-dependent, varying with cell type and tumor stage. Accordingly, high expression of PDXK and PNPO, two key genes involved in PLP biosynthesis, is associated with tumor progression in some malignancies, whereas it correlates with improved outcomes in others. This review explores Drosophila melanogaster as a useful model to investigate underlying mechanisms, bypassing the limitations of human studies. Research in Drosophila demonstrates that PLP deficiency promotes cancer by triggering genomic instability. Furthermore, a critical PLP-SHMT gene–nutrient interaction impacting oncogenesis has been established in flies, offering significant therapeutic implications. Finally, studies in Drosophila have shown that PLP deficiency can promote tumor development by also triggering the loss of heterozygosity (LOH). These findings highlight Drosophila as a powerful tool to elucidate the molecular pathways linking vitamin B6 deficiency to cancer.