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Jul 8, 2013

Genetic Screening Approach IDs New Targets for Lung Cancer

  • Because patients diagnosed with late-stage non-small-cell lung cancer often have limited treatment options, researchers are ardently working to develop new drugs, paying special attention to how individuals respond to these therapies based on their genetic makeup. But finding the cancer-associated mutations that are functionally important—and therefore prime targets—has proved difficult.

    To that end, Cancer Research UK scientists have taken a different approach than most. They are using targeted genetic dependency screens to identify the alterations that are essential for lung cancer viability.

    Writing today in the Proceedings of the National Academy of Sciences (PNAS), John Brognard, Ph.D., and his colleagues identify three such mutations—gain-of-function alterations in three kinases, FGFR4, MAP3K9, and PAK5—they’ve found by taking this screening approach. Dr. Brognard et al. note that these mutated kinases are activating toward the ERK pathway, and show that their targeted depletion via small-molecule inhibitors results in speci?c killing of lung cancer cells in vitro.

    “Our study provides a new approach that can be personalized to an individual patient’s tumor and can identify in real time potential drug targets,” Dr. Brognard said in a statement. “This new technique enables us to begin mapping the most likely gene faults that encourage these cancers to grow.”

    Added Richard Marais, Ph.D., who directs Cancer Research UK’s Paterson Institute for Cancer Research: “Understanding the genetic faults that drive each individual patient’s cancer will help to make sure they get the right treatment for their disease, at the right time.”

    “Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer” appeared online in PNAS July 8.


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