Inhibition of NAMPT and CD73 Suppresses Tumor Growth: Preclinical Findings

Synopsis

Researchers are exploring new ways to treat ovarian cancer by targeting how tumor cells produce and recycle energy. This study focused on NAD+, a key molecule for cellular metabolism, and the enzymes that control its production — NAMPT and CD73. While blocking NAMPT can deplete NAD+ and energy in cancer cells, tumors often adapt by using CD73 to convert extracellular molecules into nicotinamide riboside (NR), which helps them rebuild NAD+ and survive. Using human ovarian cancer cells and a mouse tumor model, the researchers found that combining a NAMPT inhibitor (FK866) with a CD73 inhibitor (APCP) drastically reduced tumor NAD+, NMN, and ATP levels. This dual treatment caused more tumor cell death, fewer actively dividing cells, and extended survival compared to either drug alone. These findings suggest that blocking both NAMPT and CD73 may be a promising combination therapy for ovarian and other cancers, by cutting off cancer cells’ ability to maintain their energy supply.

Journal

Oncotarget