Inducing indigestion: companies embrace autophagy inhibitors.

A utophagy, the process of “selfeating” within cells, has been controversial in cancer since it was first linked to the disease in 1999. Because autophagy can either suppress or promote tumors, depending on the context, the field has been marked by both confusion and unwillingness by drug companies to get involved in therapies. But that’s changed. A consensus is emerging that it’s the tumor promotion role of autophagy that’s important in established tumors, leading to more than a dozen ongoing clinical trials of a commercially available autophagy inhibitor. And drug companies are now rushing to start their own autophagy programs, actively looking for new and better compounds. “It’s been a total turnaround,” said Eileen White, Ph.D., an autophagy researcher at the Cancer Institute of New Jersey in New Brunswick. Although hopes are high for such drugs, doubts persist about the wisdom of inhibiting autophagy, at least in some situations. “Autophagy is, as is commonly said, a double-edged sword,” said Daniel Klionsky, Ph.D., an autophagy researcher at the University of Michigan in Ann Arbor. Evidence for widespread activated autophagy in human tumors, as opposed to cell lines, is growing but still frustratingly defi cient. And the fi eld awaits its fi rst unambiguous clinical success. But autophagy is now a hot fi eld for translational cancer research.