Article: NR and NMN Influence NAD+ Metabolism to Improve Anti-Cancer Therapy: Preclinical Findings

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Cancer Cellular Health Preclinical

NR and NMN Influence NAD+ Metabolism to Improve Anti-Cancer Therapy: Preclinical Findings

Synopsis

In human cells, NAD+ is mainly produced through “salvage” pathways that recycle precursors like nicotinamide, nicotinic acid, and nicotinamide riboside (NR). Blocking this process with the drug FK866, which inhibits the key enzyme NAMPT, showed strong anti-cancer effects in lab studies but failed to produce tumor remission in clinical trials. This study found that even low levels of extracellular NAD+ or its precursors—nicotinamide mononucleotide (NMN) and NR—can rescue cancer cells from FK866-induced death, helping explain the drug’s limited success in patients. Researchers showed that two surface enzymes, CD38 and CD73, play opposing roles in this process: CD73 helps convert NMN to NR, supporting NAD+ production and cell survival, while CD38 reduces NMN availability for this pathway. When CD73 activity was blocked, tumor cells became more sensitive to FK866 treatment. These results suggest that targeting CD73 alongside NAMPT inhibition could enhance the effectiveness of anti-cancer therapies that disrupt NAD+ biosynthesis.

Journal

Journal of Biological Chemistry

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