To confirm and extend the initial findings, the team altered genes tied to NAD + production. The resulting shift again showed that higher NADH levels meant more aggressive tumors, while increased NAD + had the opposite effect.The next logical step was to find a simple way to enhance the critical NAD + level therapeutically. So the team explored what would happen if mice with breast cancer were fed water spiked with nicotinamide, a precursor for NAD + production. The scientists found cancer development was dramatically slowed down, and the mice lived longer "In animal models at various stages, we see that we can actually prevent progression of the disease," said Felding. Next Steps Now the group is working toward human trials to learn whether nicotinamide or other NAD + precursors will have similarly impressive results in humans. Since NAD + precursors are already used for other purposes, such as controlling cholesterol levels, achieving approval for human clinical trials should be simpler than is normally the case. "It is not a totally new treatment that would need to be tested for toxicity and side effects like a new drug," said Felding. "And we already know the precursors can be easily ingested." If manipulating the NAD +/NADH ratio in humans has the same effect as in mice, the results could be profound. Such treatment could benefit people at risk of developing aggressive breast cancer, offer complimentary treatment to chemo and radiation therapy to avoid disease recurrence, and maybe even provide a preventive treatment for women with a family history of breast cancer. This research was funded by grants from the National Institutes of Health (R01CA112287, R01CA170737, R01CA170140, UL1RR025774 and R01DK053244), the US Department of Defense (W81XWH-08-0468), the California Breast Cancer Research Program (17NB-0058, 16IB-0052, 12NB-0176 and 13NB-0180), and the Susan G. Komen Foundation, as well as a donation from Las Patronas.