The potential efficacy of ω-3 fatty acids as anti-angiogenic agents in benign vascular tumors of infancy

Hemangiomas of infancy are benign vascular tumors frequently encountered in pediatrics. Medical treatment (corticosteroids, interferon, chemotherapy, embolization and radiation) in high-risk hemangioma cases could greatly benefit from the addition of new and safer therapies. The rapid growth of hemangiomas during the proliferative phase occurs secondary to a process of local uncontrolled angiogenesis, involving potent mediators such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We hypothesize that omega-3 fatty acids, naturally occurring nutrients of proven health benefit to infants, could become an alternative or an adjuvant treatment for hemangiomas, by slowing down their rapid proliferation phase through anti-angiogenic and anti-tumoral effects. Suggested mechanisms of action of omega-3 fatty acids include the downregulation of VEGF and bFGF, and the suppression of pro-angiogenic eicosanoids such as cylooxygenase-2. In this article, we review recent animal and human studies using dietary omega-3 fatty acids supplements, alone or in conjunction with chemotherapy, for the treatment of a variety of tumors dependent on angiogenesis for growth. Available murine hemangioma models offer the opportunity to determine optimal omega-3 fatty acid dose, while taking in account related immunohistochemical markers, clinical outcome and secondary effects, before planning clinical trials. Lessons learned in hemangiomas of infancy may have a broad impact in understanding the phenomenon of dysregulated angiogenesis in cancer research.