Table of Contents
Journal of Cancer Research
Volume 2014, Article ID 423401, 12 pages
http://dx.doi.org/10.1155/2014/423401
Review Article

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

1Department of Neurology, University of Cincinnati Medical Center, 260 Stetson Street, Suite 2300, Cincinnati, OH 45267-0525, USA
2Division of Hematology-Oncology, Department of Internal Medicine, UC Cancer Institute, 3125 Eden Avenue Room 2112, Mail Loc-0562, Cincinnati, OH 45221, USA
3Department of Neurosurgery, UC Brain Tumor Center, 260 Stetson Street, Mail Loc-0515, Cincinnati, OH 45221, USA
4Department of Reproductive Medicine, Cincinnati Children’s Hospital Medical Center, Mail Loc-0054, Cincinnati, OH 45221, USA
5Department of Radiation Oncology, Trihealth Cancer Institute, 4415 Aicholtz Road, Cincinnati, OH 45245, USA
6Vontz Center for Molecular Studies, 3125 Eden Avenue Room 2112, Cincinnati, OH 45221, USA

Received 20 January 2014; Revised 18 March 2014; Accepted 21 March 2014; Published 7 July 2014

Academic Editor: Takahiro Yamauchi

Copyright © 2014 Nazanin Majd et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 vitro studies have revealed that many cancer cells synthesize guanosine triphosphate (GTP), via the de novo purine 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 inhibition in vitro and in vivo. Here, we review the literature on IMPDH as related to tumorigenesis and the use of MMF as a potential antitumor drug.