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Sept. 10: The first large and comprehensive study of the genetics of a common lung cancer has found that more than half the tumours from that cancer have mutations that might be treated by new drugs that are already in the pipeline or that could be easily developed.
For the tens of thousands of Americans with that cancer — squamous cell lung cancer — the results are promising because they could foretell a new type of treatment in which drugs are tailored to match the genetic abnormality in each patient, researchers say.
“This is a disease where there are no targeted therapies,” said Dr Matthew Meyerson of the Dana-Farber Cancer Institute in Boston, referring to modern drugs that attack genetic abnormalities. He is a lead author of a paper on the study, with more than 300 authors, which was published online in the journal Nature on Sunday.
“What we found will change the landscape for squamous cell carcinoma,” Dr Meyerson said. “I think it gives hope to patients.”
The study is part of the Cancer Genome Atlas, a large project by the National Institutes of Health to examine genetic abnormalities in cancer. The study of squamous cell lung cancer is the second genetic analysis of a common cancer, coming on the heels of a study of colon cancer.
The work became feasible only in the past few years because of enormous advances in DNA sequencing that allow researchers to scan all the DNA in a cell instead of looking at its 21,000 genes one at a time. The result has been a new comprehension of cancer as a genetic disease, defined by DNA alterations that drive a cancer cell’s growth, instead of a disease of a particular tissue or organ, like a breast, the prostate or a lung.
And, in keeping with the genetic view of cancer, no one mutation in this study of squamous cell lung cancer stood out — different patients had different mutations.
As a result, the usual way of testing drugs by giving them to everyone with a particular type of cancer no longer makes sense. So researchers are planning a new type of testing programme for squamous cell cancer that will match the major genetic abnormality in each patient with a drug designed to attack it, a harbinger of what many say will be the future of cancer research.
Squamous cell lung cancer kills about 50,000 Americans each year. That is more people than are killed in the nation by breast cancer, colon cancer or prostate cancer. Well over 90 per cent of squamous cell cancer patients are or were smokers.
The new study compared tumor cells from 178 squamous cell lung cancer patients with the patients’ normal cells. More than 60 per cent of the tumours had alterations in genes used to make enzymes that are particularly vulnerable to the new crop of cancer drugs. Many of the drugs are already available or are being tested on other cancers.
These enzymes function like on-off switches for cell growth, said Dr Roy S. Herbst of Yale Cancer Center, who was not an author of the new study. When they are mutated, the switches are stuck in an on position. About a dozen companies, Dr Herbst added, have drugs that block these mutated enzymes.
Yet even though the squamous cell cancers analysed in the study often had mutations in genes for these enzymes, the genes and the mutations were different in different patients.
“Unfortunately, what the Cancer Genome Atlas has revealed is that everyone’s cancer could be very different,” said Dr William Pao, a lung cancer researcher at the Vanderbilt-Ingram Cancer Center in Nashville. The study also found a real surprise, Dr Meyerson said. About 3 per cent of the tumours had a gene mutation that might allow them to evade the immune system.
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