Targeting Cancer Metabolism
Using an innovative approach, Professor Aimee L. Edinger (Developmental and Cell Biology) and colleagues have discovered a new drug that starves cancer cells to death by disrupting two critical pathways that supply nutrients for cell growth. Their team further discovered that the drug was selectively lethal to cancer cells and not toxic to normal dividing cells, passing a critical roadblock towards therapeutic use. The results demonstrate that blocking cancer cell access to nutrients may provide a new strategy for treating cancers that are resistant to current therapeutics. The complete study was recently published online in the Journal of Clinical Investigation.
Cancer cells differ from normal cells in that they contain mutations that cause them to grow continuously. The continuous growth means that cancer cells require a high abundance of nutrients to feed their high metabolic demand. Drawing on the growing knowledge of how cancer cells re-wire metabolism to grow, Professor Edinger’s team sought a way to exploit the metabolic differences between normal and cancer cells therapeutically by developing compounds that restrict the ability of cells to acquire nutrients.
“Imagine cells as bears. During the winter, or low nutrient period, normal cells can enter a hibernation-like state to survive short periods of starvation. Cancer cells are bears that don’t know how to hibernate – when food/nutrient levels are low, cancer cells die instead of going to sleep for the winter,” said Edinger.
Professor Edinger’s studies suggest that multiple types of cancers will be sensitive to the drug, as the pathways targeted by the drug are not restricted to one specific cancer type. This is a significant finding as most tumors contain a mixture of cells with different cancer-causing defects. These genetically complex tumors can become resistant to therapies that target specialized cancer characteristics, but may be susceptible to Professor Edinger’s drug.
In addition to Professor Edinger, Seong Kim, Saurabh Roy, Bin Chen, Tiffany Nguyen, Ryan McMonigle, Alison McCracken, Yanling Zhang, Satoshi Kofuji, Jue Hou, Elizabeth Selwan, Brendan Finicle, Tricia Nguyen, Archna Ravi, Manuel Ramirez, Tim Wiher, Garret Guenther, Mari Kono, Atsuo Sasaki, Lois Weisman, Eric Potma, Bruce Tromberg, Robert Edwards and Stephen Hanessian contributed to the study.