A sweet trap for cancer

A cancer cell's sweet tooth just might be its Achilles' heel. Researchers have long observed that most cancer cells consume a lot of glucose and metabolize it through glycolysis into lactate, instead of the usual route of mitochondrial oxidative phosphorylation. Textbook wisdom held that the oxidative phosphorylation pathway must be defective in cancer cells. Now Valeria R. Fantin and colleagues at Harvard Medical School offer a new interpretation (Cancer Cell 2006, 9, 425). They report that cancer cells use the glycolysis pathway because it is essential for cancer cell growth and proliferation. Furthermore, they argue that lactate dehydrogenase A (LDH-A), a pivotal enzyme in glycolysis, might be a good protein to block in cancer drug development. Inhibiting LDH-A would thwart tumors but not normal cells, so side effects would be minimal, Fantin suggests. "There's evidence from a study in Japan that patients with a complete lack of LDH-A can live pretty normal lives," she adds. In an accompanying commentary, Thi Bui and Craig B. Thompson at the University of Pennsylvania call for "cancer biologists to dust off their biochemistry textbooks. It seems there are a few chapters that still need to be written."