Avenues of research in dietary interventions to target tumor metabolism in osteosarcoma

Osteosarcoma (OS) is the most frequent primary bone cancer, affecting mostly children and adolescents. Although much progress has been made throughout the years towards treating primary OS, the 5-year survival rate for metastatic OS has remained at only 20% for the last 30 years. Therefore, more efficient treatments are needed. Recent studies have shown that tumor metabolism displays a unique behavior, and plays important roles in tumor growth and metastasis, making it an attractive potential target for novel therapies. While normal cells typically fuel the oxidative phosphorylation (OXPHOS) pathway with the products of glycolysis, cancer cells acquire a plastic metabolism, uncoupling these two pathways. This allows them to obtain building blocks for proliferation from glycolytic intermediates and ATP from OXPHOS. One way to target the metabolism of cancer cells is through dietary interventions. However, while some diets have shown anticancer effects against certain tumor types in preclinical studies, as of yet none have been tested to treat OS. Here we review the features of tumor metabolism, in general and about OS, and propose avenues of research in dietary intervention, discussing strategies that could potentially be effective to target OS metabolism.