A hypothesis-driven synthetic lethality approach recently conducted in our laboratory revealed the extreme vulnerability of cells deficient in the BC early onset gene BRCA1 to NAD+ depletion after concurrent metformin [28] and nicotimamide phosphoribosyltransferase (NAMPT) inhibition, suggesting that the evaluation of metformin/NAMPT small molecule inhibitor combinations (e.g., FK866) to treat BRCA1-related BC may be warranted (manuscript in preparation). The gene discussed is BRCA1; the disease is breast cancer.