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The study, published in Cell Metabolism, found that MYC stimulated synthesis of purine molecules. Purines are essential for cells to produce RNA and DNA, both of which are required for growth and division. MYC-expressing cells had a particular need for a specific type of purine called guanosine.
“We were excited to discover that purine synthesis was so important for this subset of SCLC cells. There are already safe and effective inhibitors of guanosine synthesis used in patients for other diseases besides cancer. Our findings suggested that mice with MYC-expressing SCLC might benefit from treatment with drugs that inhibit purine synthesis,” said Dr. Fang Huang, a visiting scholar at CRI and first author on the paper.
To test the hypothesis, researchers treated mice from multiple different mouse models of SCLC with the drug mizoribine, a purine synthesis inhibitor. Treatment with this drug suppressed tumor growth and significantly extended the lifespan in mice with MYC-expressing SCLC.
“Our findings suggest purine synthesis inhibitors could be effective in SCLC patients whose tumors have high levels of MYC. If we are right, this could quickly provide a new treatment for this disease, which has few options at present,” said Dr. DeBerardinis.
Dr. DeBerardinis, recently selected to be a Howard Hughes Medical Institute (HHMI) Investigator, is affiliated with the Eugene McDermott Center for Human Growth and Development and the Harold C. Simmons Comprehensive Cancer Center. He is a practicing physician and Division Director of Pediatric Genetics and Metabolism at Children’s Health. He is also the Chief of the Division of Pediatric Genetics and Metabolism at UT Southwestern, where he holds the Joel B. Steinberg, M.D. Chair in Pediatrics and is a Sowell Family Scholar in Medical Research.
The National Institutes of Health, the HHMI, the V Foundation for Cancer Research, the Cancer Prevention and Research Institute of Texas, The Welch Foundation, and donors to the Children’s Medical Center Foundation supported the research.
About CRI
Children’s Medical Center Research Institute at UT Southwestern (CRI) is a joint venture of UT Southwestern Medical Center and Children’s Medical Center Dallas, the flagship hospital of Children’s Health. CRI’s mission is to perform transformative biomedical research to better understand the biological basis of disease. Located in Dallas, Texas, CRI is home to interdisciplinary groups of scientists and physicians pursuing research at the interface of regenerative medicine, cancer biology, and metabolism. For more information, visit: cri.utsw.edu. To support CRI, visit: cri.utsw.edu support.
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