It's a hard truth about cancer - one that scientists tend to talk about quietly, and among themselves: If we just keep searching for cures, we'll never really win the war.
Decades of research have revealed that cancer is not a monolithic scourge but a collection of more than 100 diseases that can be further fractured into subtypes by the genetic aberrations that underlie them. That knowledge has made it the poster child for "precision medicine," an idea that has captured the support of the White House, with the tantalizing prospect that future drug regimens will be individualized to a cancer's genetic profile.
But a growing number of scientists and physicians have begun to argue that all that knowledge points in an entirely different direction. If anything, they argue, logic suggests that an advanced disease can find an escape route from even very sophisticated targeted drugs. If saving lives, and not just extending them, is our ultimate goal, the biggest scientific opportunity right now appears to be in prevention of cancer rather than curing it once it's developed.
"It’s continually evolving and adapting to the treatments we give," said Ernest Hawk, vice president of cancer prevention at the University of Texas MD Anderson Cancer Center. "There's a large effort around targeted therapies, but they tend to prolong life and improve symptoms of life for cancer patients. Rarely does it really ablate the disease and remove the risk. It's the biology of the disease that’s telling us there’s the greatest opportunity in prevention and early detection than in treatment."
No one is suggesting we should stop developing treatments for advanced cancers, but most think prevention is sorely underfunded. Of the $5 billion spent by the National Cancer Institute last year, just under seven percent of the budget is specifically set aside for cancer prevention and control. Within the research budget, $438 million is devoted to detection and diagnosis. In private industry, the vast majority of funds are spent on developing treatments, not prevention.
That is despite the fact that anywhere from a third to half of all cancers in developed countries are preventable by interventions we already know about, whether by avoiding sun exposure or getting pap smears. Researchers have argued that if prevention became "plan A" and treatment became "plan B," with even a fraction of the energy and resources currently devoted to cures being applied to coming prevention, it could slash the deaths by cancer even more dramatically.
Let's look to the history of medical revolutions for guidance. Take polio, smallpox and deaths from a massive heart attack -- diseases that have declined, although we still lack cures for them. It wasn't the treatments, such as the iron lung or the artificial heart, that made the difference. It was vaccines, lifestyle changes, statins.
"It’s no easier now to cure a patient who has a massive heart attack than it was 60 to 70 years ago," said Bert Vogelstein, a cancer genome specialist at Johns Hopkins University School of Medicine. "The difference is that ... deaths from heart attacks and strokes decreased by 75 percent over the time period. And that’s virtually without any curing of advanced cardiovascular disease. It’s all through prevention. Curing cancer for the longest time was always the goal. But I think we could learn a lot as cancer researchers from the experience of our cardiovascular colleagues."
The problem is that the entire system, ranging from the basic science research funding to the drug companies, is biased heavily toward developing treatments. Putting more emphasis on prevention will require marked shifts in both the research paradigm and the culture.
To someone in the general public, a lung cancer researcher is a lung cancer researcher, regardless of whether they study prevention or treatment. Both have the same goal. But in reality, these two people live and work in very different worlds, using different kinds of analysis, attending different conferences, publishing in different journals. They are separated by a cultural divide, work in different kinds of institutions, and are often motivated by different incentives -- untangling the molecular details of cancer might make a scientists' career, and it might also help save lives. Or it might not.
"You win the Nobel Prize, you get to be director of the Cancer Institute, not by taking care of patients and discovering how to cure cancer but by cloning genes and discovering how Von Hippel-Lindau's disease is organized, and discovering how an oncogene works," oncologist Emil Freireich said in an interview for an oral history project. Such "discoveries are very, very important, but whether they will ever help anybody is not clear."
A similar gap exists within the medical system itself when it comes to prevention and treatment.
"Prevention and screening is conducted primarily by primary care physicians, or in specialized clinics ... mobile vans for mammograms and things like that," said Douglas Lowy, acting director of the National Cancer Institute. "Whereas cancer treatment is conducted primarily by cancer surgeons and oncologists, and they are involved less in prevention and screening."
These gaps became clear to Massachusetts Institute of Technology biologist Nancy Hopkins at a cancer conference five years ago, when she heard a scientist casually open his talk with a fact that she found incredible: Of course, he said, we know that 70 percent of cancers are preventable.
“And I thought, ‘What the hell is he talking about?’” Hopkins recalled.
She went back to her colleagues -- world leaders who were unraveling the molecular nitty gritty of cancer and had received millions of dollars in taxpayer money. They were dismissive. That was a public health statistic; they were working on the biology of the disease.
But for Hopkins, the fact that a large majority of cancers could be prevented by things we already know how to do was profoundly important. That was because her own research had begun to make her feel that the approach that had generated so much scientific excitement in her field – the idea of turning cancer into a chronic illness by developing and applying combinations of targeted drugs – was likely to be a Sisyphean task. In a simple zebrafish tumor alone, one of the post-doctoral fellows working in her lab had told her, there seemed to be about as much genetic variation as there was in the entire animal kingdom. Translation: It wasn't going to be easy to find the aberrant gene driving a tumor and shut it down.
But her growing excitement about prevention meant she had stumbled across a deep divide that is not always visible to the public. On sabbatical at MD Anderson, Hopkins talked with as many people as she could, assembling a set of graphs in the end that she hoped would convince her molecular biology colleagues of the opportunity that existed, if they only wanted to pivot to a new approach.
These were graphs very unlike the ones typically presented at cancer drug conferences. Instead of showing that a person lived three or six more months or maybe a year when they got a drug, it showed that more than one-third of cancer deaths could be halted if we just implemented preventive measures we already knew about. Think about the possibilities, she thought, if the cutting-edge science that was chipping away at pushing the survival curve just a little farther could be used to push down these bars?
Lowy, the interim director of the National Cancer Institute, said that although precision medicine is talked about almost exclusively as a way to treat disease, he also sees it having major implications for prevention, which he said was a "high-priority area."
That's in part because there's a funding gap. "There's substantial investment in the private sector for cancer treatment, and I expect that will continue," Lowy said.
Vogelstein has been at the forefront of trying to bridge the gap, bringing detailed genomic knowledge to new diagnostics that could, for example, detect colon cancer by analyzing a stool sample for aberrant DNA mutations. He has worked to show that DNA analysis of a pap smear could give a precise screen for cervical cancer but also be an alert system for ovarian cancer. It's possible more accurate, cheaper screening tools could be developed to deal with the problem of tests that can lead to false alarms.
But it isn't an easy slog convincing his colleagues to embrace prevention, too. And the larger problem may be philosophical.
"If you put a patient who has advanced cancer in remission, even if it’s just a few weeks or a few months, that’s dramatic," Vogelstein said. "You can show the patient before and after therapy. They go back to their jobs, or interact with their family, and they’re feeling well. And it is amazing, and it is very exciting. Prevention is anything but exciting. Nobody thanks you."