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But the drug’s highly targeted nature also means that it’s only effective in patients whose cancer results from a BRCA1 or BRCA2 mutation. For now, the trial’s success serves as a proof of concept that synthetic lethality offers a promising strategy for anticancer drug development. By leveraging an understanding of the molecular basis for different kinds of cancers, researchers can begin to design a panoply of personalized therapies. And the researchers believe that olaparib’s benefits may extend to other cancers characterized by defects in DNA repair.

The BRCA genes are classic examples of tumor suppressors–genes that, when absent or dysfunctional, set the stage for tumors to proliferate. Traditionally, researchers have struggled to find treatments that target tumor suppressors because it’s difficult to restore a cellular function that’s gone missing. “That has been a great problem in cancer-drug development,” says Iglehart.

Synthetic lethality offers an alternate therapeutic route to those genes. “This trial is the first time that hypothesis was tested in people,” says Iglehart. “That’s why it’s so interesting–nobody had ever developed a drug based against a tumor-suppressor gene using this concept of synthetic lethality. And they tested it in humans, and lo and behold, it worked just exactly the way you would expect it to work.”

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Credit: The New England Journal of Medicine

Tagged: Biomedicine, cancer

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