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IMAGE: This is Lawrence Kwong, Ph.D. view more 

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Credit: MD Anderson Cancer Center

HOUSTON – A powerful resistance mutation that appeared to emerge in melanoma after a patient received a targeted therapy combination, instead was lurking in the tumor all along, primed to thwart treatment before it began, researchers at The University of Texas MD Anderson Cancer Center report online at Cancer Discovery.

Researchers analyzed a series of biopsies taken before and during treatment to ferret out the pre-existing mutation and then developed a potential way to target its troublesome abilities.

The team, led by Lawrence Kwong, Ph.D., assistant professor of Translational Molecular Pathology, set out to find resistance mechanisms that arise against a combination of MEK and CDK4 inhibitors to treat melanoma that has a mutation in the NRAS gene.

The mutation, to a gene called PIK3CA, appeared initially to be an acquired resistance variation that arose after treatment. By re-analyzing the pretreatment biopsy, Kwong and colleagues were able to establish that it was rare but present from the start, hiding on one side of the tumor.

PIK3CA variant started rare, expanded rapidly

“Our study is the first to measure multiple regions in pre-treatment tumor biopsies at high resolution and then track the resistant mutation over

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