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 appreciation 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 breast or prostate or lung.
And, in keeping with the genetic view of cancer, in this study of squamous cell lung cancer, no one mutation 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 program 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, second in frequency only to adenocarcinoma of the lung, kills about 50,000 people each year. That is more than are killed by breast cancer, colon cancer or prostate cancer. While as many as 30 percent of adenocarcinoma patients never smoked, well over 90 percent of squamous cell cancer patients are or were smokers.
The new study compared tumor cells from 178 squamous cell lung cancer patients to the patients’ normal healthy cells. More than 60 percent of the tumors had alterations in genes used to make protein and lipid kinases, enzymes that are particularly vulnerable to the new crop of cancer drugs and for which many drugs are already available or are being tested in other cancers.
Kinases, explained Dr. Roy S. Herbst of Yale Cancer Center, who was not an author of the new study, function like on-off switches for cell growth. When they are mutated, the switches are stuck in an on position. About a dozen companies, he added, have drugs that block mutated kinases.
Yet even though the squamous cell cancers analyzed in the study often had kinase mutations, cells have many kinase 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 and an author of the new paper. “The field is really moving toward personalized medicine.”
The study also found a real surprise, Dr. Meyerson said, something that had not previously been seen in any cancer. About 3 percent of the tumors had a gene mutation that might allow them to evade the immune system. By coincidence, an experimental drug that unleashes the immune system was recently tested in lung cancer patients. Some of those who did not respond might have the mutation, he said.
Now the challenge is to put the findings to clinical use.
First, researchers have to establish that the mutations in question actually are essential to the tumors’ growth, said Dr. Bruce Evan Johnson, a lung cancer researcher at Dana-Farber and an author of the new paper. There are several steps: show that if the mutated gene is added to normal cells that they turn into cancerous cells, show that if the mutated gene is added to mice that they develop squamous cell lung cancers, and show that if the gene is turned off in cells grown in a laboratory, with a drug, for example, that the cells die.
Then come drug tests in patients. But if only a small percentage of patients have each of the mutations, that poses a problem. Ordinarily a few medical centers would enroll patients with a particular type of cancer, like squamous cell. But if, instead, squamous cell patients are subdivided according to their particular gene mutations, there would be too few for a drug test within a single institution or even several.
So the plan is to cast a wider net. The major medical centers intend to form a consortium. In it, each center would direct one or more studies of one mutation and one drug that might home in on the specific mutation. So even though only a small percentage of squamous cell cancer patients would have that mutation, patients across the country could be in a clinical trial of a targeted drug. A patient’s own doctor could administer the drug and the medical center directing the trial could analyze the data in partnership with the company that makes the drug.
That sort of system worked for adenocarcinoma, Dr. Johnson said, allowing researchers to test drugs that work for only 2 to 3 percent of patients.
And the work can move fast, he added. A Pfizer drug, crizotinib, which targets a rearranged gene in some adenocarcinomas, entered clinical trials in 2008 for lung cancers with the rearrangement. The results were reported in 2009 and were published in 2010. Crizotinib was approved in 2011 for patients with the gene rearrangement. The rearrangement was so rare, that about 1500 patients were tested to find 82 whose cancers had it. They were the ones included in the study.
For Pfizer, the experience was transformative. “The old way of doing clinical trials where patients are only tied together by the organ where there cancer originated, those days are passing,” said Dr. Mace Rothenberg, senior vice president of Pfizer oncology.
Dr. Johnson too sees it as a wave of the future. “That was the first time we really went after the genetic abnormality,” he said. Now, he said, with squamous cell cancer, “we are sort of where we were four or five years ago with adenocarcinoma."
As police search for a motive in a deadly Minnesota workplace shooting, witnesses say the gunman may have been fired from his job at a small signage company earlier in the day. Four people and the gunman were killed, and four others were injured. NBC's Kevin Tibbles reports. By NBC News staff, KARE 11 and wire reports. Updated at 8:02 a.m. ET: MINNEAPOLIS - A gunman killed four people inside a Minneapolis sign-making business before turning the weapon on himself, authorities said early Friday. The victims' bodies were found shortly after officers arrived at Accent Signage Systems Inc., located in a residential area in the city's north side, after receiving a 911 call Thursday afternoon, according to police spokesman Sgt. Stephen McCarty. When officers arrived and entered the business to assist with the evacuation of employees, give aid to the victims and to search for the suspect, they found four victims dead from apparent gunshot wounds," McCarty said in a statement. Four other people were wounded, including three critically. McCarty declined to identify those killed or wounded, and said he did not know what connection the shooter may have had with the business, if any. 'Kind of odd' Minneapolis Police Deputy Chief Kris Arneson said officers never fired at the shooter. She didn't release other details — including the shooter's possible motive. Neighbor Heather Buckingham, who told NBC station KARE 11 that she formerly worked for Accent Signage Systems as a receptionist, said the gunman was an employee of the firm who had been laid off on Thursday.Police continue to investigate a shooting in Minneapolis that left "several" dead and four injured. KARE's Jay Olstad reports. "The one that was doing the shooting was quiet, kept to himself," she told KARE 11. "Kind of odd." Someone from inside the building called 911 around 4:30 p.m. to report the shootings, police said. The first officers on the scene quickly began evacuating people from the business and closed off several blocks. Marques Jones, 18, of Minneapolis, said he was outside a building down the street having his high school senior pictures taken when he and his photographer heard gunfire that sounded close. "We heard about four to five gunshots," Jones said. "We were shocked at what happened and we just looked at each other. We all just took off running to our vehicles."
Craig Lassig / APA police officer stands at the entrance of Accent Signage Systems in Minneapolis on Thursday. 'Watched his boss get shot' Local resident Barb Gasterland told KARE 11 that an employee of Accent Signage Systems came to her home looking for help. "He was visibly fearful," she said. "He came running up the side of the road and asked for the phone because he was running from the shooter." Gasterland said the man described the details of the shooting while hiding in her house for about 30 minutes. "He had watched his boss get shot and his best friend and two other people," she told KARE 11. "He could tell one person was dead at least." Minneapolis Mayor R. T. Rybak described the incident as a "horrible tragedy." 
John Autey / St. Paul Pioneer Press via AP Officers with the Minnesota State Patrol man the Penn Avenue bridge over Bassett's Creek near the scene of a shooting in Minneapolis on Thursday. In a statement, Governor Mark Dayton said: "I deplore this senseless violence. There is no place for it anywhere in Minnesota. I extend my deepest condolences to the families and friends of the innocent people killed or wounded." Local business publication Finance & Commerce reported that U.S. Under Secretary of Commerce Francisco Sanchez visited Accent Signage Systems in August in a trip focused on exporting, and praised the company for its innovation.