The vulnerable cancer cell(ells. We don't have all the answers yet...),Health

In the experiments reported in Cell, Elledge and his colleagues used an RNAi technique developed by Elledge and HHMI investigator Greg Hannon at Cold Spring Harbor Laboratory. "Overall, we were asking very simple questions: What do RAS cells need to survive? And is it different from what normal cells need to survive?" said Elledge.

Elledge's team generated about 75,000 bits of short hairpin RNAs that can be inserted into retroviruses. When the altered retroviruses infected either normal cells or cells that differed by only a single mutation in KRAS, the shRNA bound to corresponding stretches of RNA in the cells, and prevented their translation into proteins.

If the shRNA knocked down production of a protein essential to keeping the cells alive, then the abundance of that particular shRNA quickly diminished as cells died. The researchers could track the identity of the shRNA and its corresponding gene by using a "barcoding" method to track the diverse pool of short hairpin RNAs in parallel. In the barcoding method, every short hairpin RNA that is made carries a unique genetic tag. This tag lets the researchers track the effect of thousands of the RNAs in a single pool of cells in a single lab dish. "These are experiments a single researcher can perform in their own lab without the need for complex robotic platforms," said Elledge.

By tracking the abundance of each shRNA from the total pool and comparing cancer cells to cells from normal tissues, Elledge and his colleague Ji Luo identified many genes that KRAS is dependent on. In this manner, they were able to do a genome-wide survey, uncovering many new potential drug targets, including PLK-1, STK33, and a number of proteins involved in mitosis. "It will take some time to figure this out, but RAS is clearly h
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