A Review of the Potential Utility of Mycophenolate Mofetil as a Cancer Therapeutic

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Tumor cells adapt to their high metabolic state by increasing energy production. To this end, current efforts in molecular cancer therapeutics have been focused on signaling pathways that modulate cellular metabolism. However, targeting such signaling pathways is challenging due to heterogeneity of tumors and recurrent oncogenic mutations. A critical need remains to develop antitumor drugs that target tumor specific pathways. Here, we discuss an energy metabolic pathway that is preferentially activated in several cancers as a potential target for molecular cancer therapy.In vitrostudies have revealed that many cancer cells synthesize guanosine triphosphate (GTP), via thede novopurine nucleotide synthesis pathway by upregulating the rate limiting enzyme of this pathway, inosine monophosphate dehydrogenase (IMPDH). Non-proliferating cells use an alternative purine nucleotide synthesis pathway, the salvage pathway, to synthesize GTP. These observations pose IMPDH as a potential target to suppress tumor cell growth. The IMPDH inhibitor, mycophenolate mofetil (MMF), is an FDA-approved immunosuppressive drug. Accumulating evidence shows that, in addition to its immunosuppressive effects, MMF also has antitumor effects via IMPDH inhibitionin vitroandin vivo. Here, we review the literature on IMPDH as related to tumorigenesis and the use of MMF as a potential antitumor drug.