Editor's note: This is the first installment of a 2-part series.
When Nobel Prize winner James Watson, PhD, criticized the cancer establishment as too conservative in its approach to the disease in a recent article in the journal Open Biology, the media and cancer community took note.1
Dr. Watson, codiscoverer of the double helix structure of DNA, who has worked on unraveling clues to cancer's development for more than 50 years, offered the following critique of the current state of research: “The biggest obstacle today to moving forward effectively towards a true war against cancer may, in fact, come from the inherently conservative nature of today's cancer research establishments. They still are too closely wedded to moving forward with cocktails of drugs targeted against the growth-promoting molecules...of signal transduction pathways instead of against Myc molecules that specifically promote the cell cycle.”
The “war on cancer,” he argues, has not lived up to its promise of beating the disease, because most lung cancers today are as incurable as they were 40 years ago, and many other carcinomas and sarcomas remain incurable. “Even though an increasing variety of intelligently designed, gene-targeted drugs now are in clinical use, they generally only temporarily hold back the fatal ravages of major cancers such as those of the lung, colon, and breast that have become metastatic,” he added.
Dr. Watson also criticized the lack of funding and lack of a true leader in the war against cancer, along with the cancer research community's slow pace. Of the latter, he noted, “If we continue to move forward at today's never frantic, largely 5-day working week, the never-receding 10–20 years away final victory that our cancer world now feels safe to project will continue to sink the stomachs of informed cancer victims and their families.”
In an interview following the piece's publication, Dr. Watson elaborated on some of his frustrations, stating that more efforts should be directed toward targeting cancer stem cells, which are much more resistant to therapy. In addition, he believes investigators need to explore the potential role of antioxidants in adversely affecting cancer treatments. “It's been my life's ambition to see cancer cured,” he says. “I'm unimpressed with extending life for another month. People don't really want to say how bad it is.” Researchers' focus on treating early-stage cancers neglects the most important piece of the puzzle, he says, adding, “The cancer world is not trying to cure incurable cancer. They need to concentrate on late-stage disease.”
A Complex Problem
CancerScope asked several other leaders in the community to weigh in on the current state of cancer research.
Susan Love, MD, breast cancer and women's health advocate, agrees that the way research is selected and conducted doesn't allow for many new ideas, and that there is a “herd effect” in terms of areas on which researchers concentrate. The downside of peer review is that they tend to keep funding the same kind of research, she adds.
Targeted therapy, with a few exceptions, has not been very successful, says Dr. Love, because cancer cells can always adapt and find a different pathway. What hasn't been pursued as much is thinking about the cancer cell in its macro- and microenvironment. “It's not just the genetic abnormalities of the cancer cell but also the reaction of cells in the body and the entire immune system,” she says. “It's much more complex than one pathway.”
Dr. Love also believes more work should be put into exploring viruses that may contribute to cancer, pointing to what she considers to be the biggest cancer success story of her lifetime: the human papillomavirus vaccine and cervical cancer. The entire system–from researchers to funding institutions– contributes to the lack of truly unique research, she says. “You go into the field saying you want to cure cancer, but then you have to get a PhD and you're working in someone's lab and you have to get funded,” she says. “So you do something a little different from your mentor but not a lot, and then you have to get tenure. And getting grants becomes as much the goal as finding the answer. By the time you get tenure, you forget you were going to solve cancer.”
None of this problem is new, she adds. It is typically the way science works. So, people who have a different idea outside of the mainstream often will have to find alternative funding sources.
One way to encourage such types of research is through advocacy groups. This type of effort has a chance of, if not completely changing the system, at least “giving it a counterbalance” by developing alternative ways of funding research. Originally, money raised by the breast cancer advocacy movement was awarded directly to scientists without much public or patient input. “We thought if we raised the money and handed it over to the scientists, it would solve the problem for us, but it didn't happen,” Dr. Love says. “Even the Department of Defense's breast cancer research has advocates at every level of peer review, and that has helped. But it's not enough.”
Breast cancer advocates such as Dr. Love are trying to encourage new approaches to research. For example, the Army of Women that her organization has developed, which includes more than 370,000 women across the country willing to participate in breast cancer research, makes human subjects available to scientists in an effort to encourage more human studies versus research in mice. “The mice are nice, pretty science, but it doesn't always translate very well to humans,” she says. “We continue to be successful in recruiting women for all kinds of research, not so much for clinical trials but for figuring out how breast cancer works.”
In addition to involving the public more, Dr. Love's group wants to encourage more work into the basic anatomy of the breast, much of which still is unknown. Further, a concentration on new drugs to treat cancer, rather than a focus on ways to prevent it through methods such as vaccines, should not be the main answer because the drugs have significant collateral damage, she says. “We have to keep prodding,” she adds. “The old approach of researchers saying, ‘We'll call you when we have the answer’ [is] not going to fly anymore.”
Funding and Regulations
Otis W. Brawley, MD, chief medical officer of the American Cancer Society (ACS), believes the two biggest problems in medical research are the low levels of funding and the multitude of institutional review board (IRB) regulations and restrictions. “The low level of funding at the 10% pay line forces people to be more conservative,” he says. “People are going to submit grants that reviewers believe are truly achievable, and the researcher who hasn't adopted that approach is committing professional suicide.” At the same time, the cumbersome IRB regulations “have become so burdensome, they are impeding good science,” he says.
He does believe there is some good news on the research front. The ACS annual report on cancer rates points to a 20% reduction in the US cancer mortality rate from 1991 to 2009, much of it due to prevention efforts such as lower smoking rates (see “Cancer Mortality Declines 20% Since 1991,” next page).2 For that reason, prevention research needs to be better funded, he says.
In addition, new drugs are available to treat colon cancer, and both colon and breast cancers have experienced more than 30% reductions in mortality. Scientists also have a much better understanding of how the cancer cell operates. Groundbreaking treatments have emerged, including Gleevec for chronic myelogenous leukemia and crizotinib for ALK-mutated lung cancer. The latter was the result of lymphoma and thyroid cancer research.
“I'm frustrated with every new drug that increases median survival for 2 to 3 months,” he says, “but at the same time, we're increasing our understanding of what goes on in the cancer cell. And that will ultimately help us beat the disease.”
His biggest concern is the number of young investigators who are leaving the field because they cannot get funding. The average age of a National Institutes of Health (NIH)-funded investigator is rumored to be 45, he says, noting that when 1 in 10 grants is funded, they are more likely to be awarded to seasoned veterans. Although NIH used to reserve funds for scientists who were within 6 to 8 years of the start of their careers, this money went away with budget reductions and has never been replaced.
Part 2 of this article, which will appear in the May 15 issue, will include more perspectives on the challenges of tackling cancer.