It’s a measure, perhaps, of what a quagmire the war on cancer has become that the basic premise of the whole enterprise — that this is about reducing mortality, saving lives — requires repeating.
One Small Victory at a Time
As if the non-small-cell lung cancer that had defied conventional therapies had not been enough, the tumors in and around Tom Stanback’s lungs grew so large that he was having difficulty swallowing and breathing. Unwilling to go quietly, Stanback actively sought out clinical trials (surprisingly, most patients don’t) in search of anything that might extend his life. One of them, at Johns Hopkins in Baltimore, is focused on studying the enzymatic on/off switches that sit atop the underlying genome and regulate whether and how loudly those genes will be expressed. This includes the mutated genes that crank out cancer cells. While science can’t do much to change the genome, epigenetic functions are manipulated all the time — sometimes inadvertently, by exposure to environmental chemicals, say; other times cleverly, by drugs. Stanback, a 62-year-old, 40-year former smoker, was involved in a trial to see if a new epigenetic drug could shrink his tumors.
In his case, the answer was no, not quite. But the leaders of the cross-disciplinary, cross-institutional research team behind the work (one of nine, soon to be 10, main teams backed by SU2C) weren’t finished. They postulated that even if the epigenetic manipulation alone didn’t knock out the cancer, it had a priming effect, improving the likelihood that other treatments administered later would work. That’s exactly what happened when Stanback returned home for a round of radiation therapy at Memorial Sloan-Kettering Cancer Center in New York City and joined a second clinical trial. His tumors have shrunk markedly in the past year and a half and were not visible on a recent CT scan. “The drug nudges the T cells to being alive and active,” he says. “I’m alive. I’m healthier than I’ve ever been.” Even better, a few other patients in the study have enjoyed what appears to be complete remission.
The team behind these victories is led by Dr. Stephen Baylin, an oncologist at Johns Hopkins, and Dr. Peter Jones, a biochemist and molecular biologist at the University of Southern California. They ride herd on a diverse group of experts — geneticists, pathologists, biostatisticians, biochemists, informaticists, oncologists, surgeons, nurses, technicians and specialists who normally wouldn’t have been working as an ensemble. The team was awarded its grant in May 2009 and within the year was able to extend the epigenetic clinical trial that enrolled Stanback and launch new ones. That is light speed in modern research — the lab to clinic cycle in cancer is typically a decade.
This kind of institutional transformation is not easy, but it’s the only way to take advantage of the dazzling scientific and technological advances that have taken place in just the past three years — advances in bioengineering, nanotechnology, drug compounds and data gathering, including protein data, splicing data and mutation data, all of which is being hoisted into view by ever cheaper computational muscle. Sequencing the first human genome took more than a decade and $2.7 billion. Today sequencing can be done for a few thousand bucks in a few hours.
That progress has led to similar pharmaceutical leaps. Hundreds of drug agents are in development for therapies targeting the genetic mutations that have thus far been identified. Some, as in the case of Stanback’s trial, seek to reactivate the body’s immune system. Others are designed to cut off a tumor’s blood or energy supply; still others seek to restart apoptosis, the programmed cell death that normally takes place in healthy bodies. New biomarkers are allowing doctors to identify, target and track cancer cells. “It happened, and it happened quickly,” says DePinho. “If you look back on the progress that we made, it was against not having a periodic table of cancer, of not being able to understand genes, of not being able to model.”
DePinho’s use of the moon-shot analogy is not a marketing gimmick. In 1961, when President John F. Kennedy announced that the U.S. was going to the moon, the idea was no longer science fiction. The physics were understood. What remained was a giant engineering project: apply enough money and aerospace engineers and you eventually get to Neil Armstrong’s giant leap for mankind. When President Richard Nixon announced the war on cancer in 1971, victory wasn’t remotely possible. It was as if someone had announced a moon shot in 1820, says Cantley.
Today the physics of cancer are known; what remains is massive engineering. “In the old days, everyone knew it took 30 years to test a compound,” says Dr. Daniel Haber, director of the Massachusetts General Hospital Cancer Center. Scientists got that to an eight-to-10-year process. Teams of researchers have whittled it down to a two-year timeline from the discovery of a specific mutation to a drug to treat it. That’s fast by most measures — but not fast enough if you’re a patient. Says Haber: “Cancer doesn’t wait two years.”
Despite that urgency, shifting to a team model will not happen overnight, in part because the sociology of medical research isn’t, in fact, very social. Historically, the principal investigator wins grant money for a proposal and takes top billing on everything from publications to patents to the glory that goes with them. Those in turn are crucial to getting more grants. It is self-perpetuating and self-limiting and over the past decade has increasingly stifled young investigators in particular because the percentage of grant applications that are funded by NIH, the so-called pay line, is now below 10% and falling.