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 in 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 mutation, to a gene called PIK3CA, appeared initially to be an acquired resistance variation that arose after treatment. By reanalyzing the pretreatment biopsy, Lawrence Kwong, assistant professor of translations molecular pathology, and his colleagues were able to establish that it was rare but present from the start, hiding on one side of the tumor.
"Our study is the first to measure multiple regions in pre-treatment tumor biopsies at high resolution and then track the resistant mutation over years of treatment through six biopsies," Kwong explains. "We are able to say that this mutation started out rare and then...