Jason Sheltzer thought he was learning answers to a simple question, but one that, for cancer patients, could mean the difference between life and death: Which genes can’t tumor cells survive without? Identifying DNA that seems essential to cancer cells’ survival tells drug developers which genes or gene products to target — a tried-and-true approach that has led to such lifesaving cancer drugs as Herceptin.
But the research took an unexpected turn. Working with human cancer cells growing in a dish, Sheltzer, a biologist at Cold Spring Harbor Laboratory, and his colleagues used CRISPR genome editing to knock out DNA that more than 180 previous studies had identified as essential in various forms of cancer. Those studies concluded that the tumors can’t survive without the proteins made by these genes. But in DNA-knockout after DNA-knockout, Sheltzer’s team found, the cancer cells kept on despite the lack of an “essential” protein. It was like a car from which the carburetor had been stolen speeding down the highway unfazed.