Researchers speculate that cancers may be more complex that they knew. And that's why a single tissue sample taken from a single tumor may not be the best way to figure out a course of treatment they claim.
British researchers took multiple samples within kidney tumors (before and after drug treatment) and also got samples from tumors that had spread from the original cancers in four patients. They performed all kinds of genetic tests, including detailed DNA sequencing, on the cancers and found wide variations in some key traits.
“We used every possible genomics technique available,” senior author Charles Swanton. “Even then we are only scratching the surface of the complexity within each cancer.” Those results help explain why some treatments that seem like a good idea may not work. “It's a sobering finding,” Andrew Futreal, who until recently was director of cancer genetics and genomics at Wellcome Trust Sanger Institute in London and co-author of the study told The Wall Street Journal. The work was published in the latest New England Journal of Medicine.
In an editorial accompanying the study, Dan L. Longo, an editor at the journal, suggested the varied genetic makeup of tumors described in the study stands in contrast to “overoptimism” among proponents of personalized medicine. The editorial invokes Albert Einstein to explain why the highly technical results matter. “Everything should be made as simple as possible, but no simpler,” he was reputed to have said. The report indicates that matching tumors and treatments based on genetic characteristics won't be as simple as some suggest, he wrote.
Still, the scientists were able to figure out some traits found on the original tumors that were consistent in many samples. Those may be among the ones to focus on in the future. The findings don't diminish enthusiasm for the idea that genetic knowledge about tumors can transform cancer care, the researchers said. But it could make personalized treatment more complex—and more costly.
In the study, led by Marco Gerlinger and Charles Swanton at the London Research Institute, researchers obtained tumor tissue from four patients with kidney cancer. Using DNA sequencing and other techniques, they obtained genetic profiles from as many as nine places in one sample from the original tumor and three from sites where the tumor had spread, or metastasized.
Among the findings: Only about one-third of 128 mutations they detected were present in all of the sites studied. In addition, they identified in a single tumor a genetic signature associated with a good prognosis—and another linked to a poor one. Moreover, there were significant differences between mutations in the original tumor and the site of metastasis, suggesting the need for additional biopsies as a patient's cancer progresses. With a single biopsy, “you might miss the connection between the mutation and whatever outcome you are looking at,” said Dr. Futreal.
The researchers cautioned that the study was done in only one type of cancer, and that more research is needed to see how much genetic variation there is in other types of tumors.
Scott Kopetz, who specializes in gastrointestinal cancer at M.D. Anderson, said the research underscores the need to test patients' tumors at the time of treatment since Dr. Kopetz said getting additional biopsies from patients could be costly and inconvenient for patients, but the tumor discovered at diagnosis “may be very different from the tumor that is threatening their lives here and how.” Some of the differences may be the result of the initial treatment of the tumor and others “because [the cancer] has spread and gone to different locations in the body.”
The findings describe in more precise detail what many cancer doctors and researchers have long been aware of, said Jennifer Litton, a breast cancer specialist at M.D. Anderson Cancer Center in Houston who wasn't involved in the study. Tumors “are really like a moving target,” she said. “As they are growing or when they're exposed to different drugs, they change” from their original form. “That's what we're struggling against when we try to eradicate metastatic disease.”
The study was funded by the U.K.'s Medical Research Council and other cancer organizations as well as Novartis SA, which is sponsoring a broader study of one of its drugs that the four patients were enrolled in.
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