Cancer scans may provide false picture of genes

Cancer DNA tests give only a partial picture of the genes driving the disease, according to a study that throws cold water on the idea that scanning may quickly lead to highly effective personalized treatments.

Multiple scans on kidney tumors determined that mutations in each portion of the malignancy varied wildly, with only one-third of anomalies found in all parts, according to a report in the New England Journal of Medicine.

If confirmed in other cancer types, the finding suggests doctors and companies have only a limited ability to precisely identify individual mutations that can be targeted with drugs, since their tests are typically based on a single biopsy sample. It may also explain why cancer becomes resistant to gene-targeted medicines, the U.K.-based investigators said.

The result points to “a serious flaw in the imagined future of oncology,” wrote Dan L. Longo, a cancer researcher and deputy editor of the journal, in an accompanying editorial.

The researchers also performed an experimental prognostic test that looked at levels of 110 genes on different samples from a patient’s cancer, according to the report. When the test was done on one part of a tumor, the disease was judged to have a favorable prognosis. When the same scan was performed on another section, the cancer had an adverse prognosis.

Devising nonstandard drug regimens based on the result of a single gene test “should be applied with great caution until more is known,” said Charles Swanton, an oncologist at Cancer Research U.K. London Research Institute and the senior study author. It could lead to harm if the patient gets prescribed a drug that hits a gene mutation that turns out not to be present in most of his tumor, he said.

The tumor variability could also explain why cancer becomes resistant to gene-targeted drugs, according to Swanton. The resistance mutations may be present from the start in some parts of the tumor.

Barrett Rollins, chief scientific officer of the Harvard University-affiliated Dana-Farber Cancer Institute in Boston, said the finding doesn’t undercut current practice. While variability is an issue, many cancers now respond to drugs targeted at specific genetic features, he said.

“I’d be disappointed if the inference from this study is that targeted therapies are useless,” Rollins said in a telephone interview. “They’re not useless, they’re just not useful enough.”

Cancer genetics is so complex that researchers may never completely grasp it, Rollins said.

“Until we understand that whole universe of mutations, we’ll have to treat what we find and test to see whether it works,” he said.

Brian Druker, the doctor and cancer researcher who helped develop Gleevec, an early gene-based leukemia medicine made, said the analysis shows the need for “better tools to identify cancer at earlier stages, when it is far less complex.”

Druker directs the Knight Cancer Institute at the Oregon Health & Science University in Portland.

Personalized medicine “is going to be much harder than we hoped,” said Andrew Futreal, a study co-author who is starting a new job at the University of Texas MD Anderson Cancer Center in Houston later this month, in a telephone interview.

“If you stick a needle in the right side of the tumor, you could miss a key mutation in the left side,” he said.

One crucial question is whether lung cancer, breast cancer, and other common cancer types are as variable as kidney cancer was found to be, said Futreal.

Ongoing large-scale cancer genome studies could provide clearer answers in a year or two, he said.