(P12-015-25) Ultra-High Dose Oral ω3 Docosahexaenoic Acid (DHA) or Eicosapentaenoic Acid (EPA) Block Tumorigenesis in a MYCN-Driven Neuroblastoma Model

Objectives: Neuroblastoma remains one of the most challenging pediatric cancers, accounting for 15% of childhood cancer deaths despite representing only 8% of cases. High-risk cases face particularly poor outcomes, with less than 50% survival rates, dropping to just 5% in relapsed cases. The current standard of care relies heavily on genotoxic treatments, creating an urgent need for more effective and less toxic therapeutic options.

Methods: We employed a prophylactic syngeneic mouse model to evaluate the effects of high-dose lipid mediators on tumor development. Omega-3 fatty acids (EPA, DHA, or oxidation-resistant deuterated DHA [D-DHA]) were administered at human-equivalent doses of 12.3-14.6 g/d, or arachidonic acid (ARA) at 4.6-6.0 g/d through oral gavage. Seven days post-treatment initiation, MYCN-expressing murine neuro-2a cells were injected subcutaneously. Treatment continued for 10-20 days before tissue collection and analysis.

Results: Control groups showed 50% tumor formation (4/8 animals) at approximately 10 days. High-dose omega-3 treatments (DHA, D-DHA, and EPA) completely prevented tumor formation in all treated animals (n=8 or 10). Conversely, ARA treatment increased tumor incidence (6/10 animals) and accelerated onset (5.5 vs. 10 days). Combined ARA/EPA administration resulted in a tumor burden similar to control levels, suggesting EPA directly counteracts ARA's tumor-promoting effects. The study also suggests that DHA's anti-tumor activity operates through non-oxidative mechanisms. Previous studies of omega-3 using doses in humans below 4 g/d may have been too low to warrant use as a primary treatment.

Conclusions: These findings suggest that ultra-high doses of omega-3 fatty acids, particularly DHA and EPA, may represent a promising low-toxicity therapeutic approach for neuroblastoma treatment, with implications for similar cancers.

Funding Sources: N/A