Researchers at Winship Cancer Institute of Emory University have discovered that an apparent “dead end metabolite” has a previously unknown function regulating cell growth. The finding could guide efforts to target cancer cells’ warped metabolism with selective drugs.
Jing Chen, PhD, professor of hematology and medical oncology at Emory University School of Medicine, has led the study on the oxidative pentose phosphate pathway, which supplies both cellular building blocks for rapid growth and a critical internal antioxidant called NADPH. Flow through the pentose phosphate pathway is generally increased in several types of cancer cells.
The first enzyme in the pathway, called G6PD (glucose-6-phosphate dehydrogenase), generates a chemical called 6-phosphogluconolactone, which was thought to be a metabolic dead end. Targeting G6PD does not pinch off growth in other cancer cells with relatively high levels of SOD2. SOD2 levels could be a good marker to predict the response to treatments targeting G6PD, Chen says.
The co-first authors of the paper are Emory postdoctoral fellows Xue Gao, PhD, Liang Zhao, PhD and Shuangping Liu, PhD. Zhao and Liu are currently at Xiangya Hospital, Central South University and Dalian University in China.