Nordihydroguaiaretic acid (NDGA), a lignin compound from creosote bush, demonstrates significantly enhanced anti-cancer activity against prostate tumors when paired with EZH2 inhibitors, working through the NRP1 pathway to modify epigenetic marks that control tumor growth. The combination therapy approach targets both direct tumor suppression and the chromatin remodeling mechanisms that cancer cells exploit for survival. This dual-pathway strategy represents a meaningful advance in precision oncology, particularly for hormone-resistant prostate cancers where conventional therapies show diminishing returns. NDGA has attracted research interest for decades due to its antioxidant properties, but this epigenetic angle reveals previously unknown therapeutic potential. The NRP1 involvement is particularly noteworthy since this receptor pathway influences both angiogenesis and neural development, suggesting broader applications beyond prostate cancer. However, the practical translation remains challenging given NDGA's historically poor bioavailability and the need to establish optimal dosing ratios for combination therapy. The approach reflects the growing sophistication of epigenetic medicine, where researchers identify synergistic combinations that can overcome individual compound limitations while targeting multiple cancer vulnerabilities simultaneously.