A research team led by UT Southwestern Medical Center scientists has identified an atypical（非典型的） metabolic¹ pathway unique to some tumors, possibly providing a future target for drugs that could reduce or halt the spread of cancer. Dr. Ralph DeBerardinis, senior author of the study published Nov. 20 in Nature, likened the newly discovered pathway to traffic that is rerouted during a highway construction project.

"If we hone in on this reverse pathway, then we may be able to prevent the growth of certain types of cancer," said Dr. DeBerardinis, assistant professor of pediatrics（小儿科） and a physician scientist in the Eugene McDermott Center for Human Growth and Development. "It's long been thought that targeting tumor-specific metabolic pathways would lead to an effective way to treat cancer. This is one of the few metabolic pathways that may actually exist specifically in tumors."

The pathway involves the Krebs cycle, a series of chemical reactions that generates energy and is considered one of the most familiar and widely studied processes in biology. In the normal cycle, energy is derived² by the breakdown³ of acetate from ingested（摄取，咽下） carbohydrates⁴, fats and proteins into carbon dioxide and water.

For more than 70 years, biology textbooks have depicted⁵ the Krebs cycle as running clockwise in normal cells. UT Southwestern researchers found that in some tumors the cycle runs in reverse.

The discovery is the latest milestone⁶ in a long line of scientific inquiry⁷ that began in the 1920s when biochemists first recognized metabolic differences between cancer cells and normal cells. Scientists since have thought they could stop the growth of cancer cells with drugs that target only tumor-specific pathways, leaving normal cells unaffected.

Researchers have identified only a few such therapeutic⁸ windows, the latest of which appears to be the reverse Krebs cycle pathway identified by Dr. DeBerardinis and colleagues in this investigation⁹.

"There is no pathway that has been more extensively studied over the years than the Krebs cycle," Dr. DeBerardinis said. "The fact that with relatively¹⁰ modest manipulation, it can run in reverse is incredibly fascinating."

Dr. James K.V. Willson, director of the Harold C. Simmons Comprehensive Cancer Center, said the findings are significant.

"We are learning that certain cancers have previously¹¹ unrecognized mutations in genes¹² controlling metabolism¹³ -- and these abnormalities are providing new therapeutic opportunities," he said.

Andrew Mullen, a graduate student in genetics and development at UT Southwestern, was first author of the paper. Other UT Southwestern researchers involved in the study were Dr. Eunsook Jin, instructor¹⁴ in the Advanced Imaging Research Center; Pei-Hsuan Chen, graduate student in integrative（综合的） biology; and Dr. Tzuling Cheng, a postdoctoral researcher in pediatrics. Scientists from Northwestern University and from the National Cancer Institute also participated.

The project was funded in part with a grant from the Cancer Prevention and Research Institute of Texas.