Olufunmilayo I. Olapade, MD; Vincent T. DeVita, MD; Graham C. Walker, PhD
Against a changing background of major achievements and unfinished business, the American Cancer Society held a one-hour science symposium to mark its 100th anniversary.
“Research is what we need to finish this fight,” said ACS President Vincent T. DeVita, MD, Professor of Medicine at Yale University Cancer Center and a former director of the National Cancer Institute, noting that the ACS has funded 46 scientists who went on to become Nobel Laureates.
No More ‘Black Box’
Cancer initially was a “black box,” he added, and “now we can see what's going on inside.” DeVita cited progress in survival—a result of seeing into the black box—as a major achievement, stating, “When I started in the field, cancer was largely incurable.” Today, two out of three people diagnosed with cancer survive at least five years, according to ACS statistics. DeVita called the progress against cancer “an exhilarating experience,” and said, “It's quite a change, and we got there by research.”
ACS Chief Medical and Scientific Officer Otis W. Brawley, MD, agreed that the 20 percent decline in mortality among U.S. cancer patients since the early 1990s is a major achievement that should be celebrated. He stressed that this decline is due in part to the fact that today “we know some of the causes of cancer,” and that this understanding has led to cancer prevention efforts.
“Prevention is where we've gotten the most bang for the buck,” he said, citing ACS anti-smoking programs as particularly effective on the prevention front. ACS efforts have helped to lead to a more than 50 percent drop in smoking since the 1960s, which in turn has contributed to a drop in overall lung cancer death rates.
An emphasis on basic research and on the funding of young investigators have been two ACS hallmarks that have really paid off, said Graham C. Walker, PhD, an ACS Professor and Howard Hughes Medical Institute Professor at Massachusetts Institute of Technology.
Graham, a biologist known for his work on the structure and function of proteins involved in DNA repair and mutagenesis, called himself a “living example” of how funding of basic research has helped to unravel the mystery of cancer.
This basic research has shown that “cancer is a disease of mutations and changes in the DNA,” he said, adding that research has also shown that “living organisms respond to DNA damage by changing their gene expression.”
Another area of major ACS progress has been in developing and updating evidence-based guidelines for cancer screening and early detection, said David F. Ransohoff, MD, Professor of Medicine and Epidemiology at the University of North Carolina. Ransohoff, an expert in colon cancer screening, said that cancer screening has become much more complex as the evidence base has become more solid.
For example, it used to be assumed that all cancer screening tests were good and they were embraced without question, but subsequent research, has now shown, of course, that screening can have harms as well as benefits, he said, citing overtreatment for prostate cancer due to a PSA reading as an example.
Today, informed consumers no longer embrace cancer screening tests uncritically, Ransohoff continued. People want to know what the results of a screening test mean, what the implications are for treatment (or no treatment), and what scientific evidence the test is based on.
“The problem is not screening; it's what we do once we've found something. Some things we label ‘cancer’ and we scare people to death” when the prognosis is not entirely clear, he noted, citing DCIS and prostate cancers as examples. He predicted that the interpretation of cancer screening tests will increasingly become much more tailored to the individual patient, as will treatment recommendations.
Olufunmilayo I. Olapade, MD, Distinguished Service Professor of Medicine and Human Genetics at the University of Chicago, also cited cancer prevention as an area of major progress: “We're living longer, cancer is a disease of getting older,” and prevention is going to become more and more important. She pointed to research identifying the connection between BRCA1 gene mutations and a high risk for hereditary breast and ovarian cancers as a major leap forward in the war on breast cancer.
Olapade said she remembers sitting in the audience as a postdoctoral student and hearing scientists present on high-risk women and BRCA1 and thinking, “How can they be so sure?” Olapade cited the decision of Angelina Jolie to have prophylactic mastectomies because of her high-risk genetic profile and family history as an “exciting” example of just how far prevention of certain breast cancers has come: “We've known that worked since 1997,” she said of the decision. “These are cancers that grow faster.”
Olapade said that today, because of research, women at high risk of breast cancer because of BRCA mutations can elect to have prophylactic mastectomies or choose to be monitored frequently with MRI.
As for disappointments, Brawley said that when he entered the field of oncology in the mid-1980s, he expected that there would be cures for solid tumors by the 1990s. “But that has not happened.” He said he was also disappointed that the Ras gene,” the most common oncogene in human cancers, has not been able to be controlled. Ras is involved in signal transduction, and overactive Ras signaling can lead to human cancers. Somatic mutations in Ras were first identified in human cancers about 30 years ago.
Brawley also expressed disappointment that access to what is known about how to diagnose, prevent, and treat cancer has not been available to all Americans. He noted that while 1.2 million lives have been saved from death due to cancer over the last several decades, another 1.2 million probably could have been saved if those deceased people had had access to state-of-the-art technology in cancer diagnosis and treatment.
DeVita said he was disappointed at the long lag time from scientific discovery in the laboratory to application in clinical medicine. He said that because of logistical problems, the flow of information from the lab bench to the cancer patient's bedside has never been as smooth or as timely as researchers would like.
Olapade said her biggest disappointment has been that there is not as much collaboration between researchers, the public, and private sectors and patients as she would like. “People really work in silos,” which hinders research, she said. “We have to break down the silos.”
She cited major divides in medical centers between basic scientists, clinical scientists, and population scientists—divides that she said are not helpful to the war on cancer and to cancer patients. “Patients want their data shared,” she said, and silos are not conducive to data-sharing.
5 Key Goals
Symposium speakers named the following as five key goals for future progress against cancer:
1. Strong funding support for young investigators. “They're our seed corn and our future,” said Walker. He said many young investigators are very frustrated at the low funding pipeline for cancer research, and he called current federal research funding cuts “catastrophic.” Olapade agreed: “We must fund young investigators; that's the only way to bring renewal to our field.”
2. A greater emphasis on cancer prevention. Brawley said he was very concerned that over the next 10 to 20 years obesity could overshadow smoking as a preventable cause of cancer. He said healthy diets and lifestyles that stress physical activity are going to have to become more and more urgent as U.S. priorities. Walker added that scientists are just on the verge of understanding obesity on the molecular and cellular levels, which might lead to preventive treatments—much like statins for cardiovascular disease.
3. Renewed efforts to develop evidence-based cancer screening guidelines. “I suggest a very major opportunity for the ACS to lead in this field,” said Ransohoff. He noted that consumers are going to demand high--quality screening guidelines based on strong underlying scientific principles.
4. Tightly linking cancer screening to treatment. “We really haven't tied screening to treatment,” said Olapade. “We've put the burden on the patient for treatment.” Therefore, she said, there are women walking around with diagnosed lumps in their breasts that have not been treated. “Don't screen unless you can treat,” Olapade emphasized. “Get people screened, get them to the doctor, and get them treated in a way that makes sense.”
5. Increasing individualization in cancer care based on increasing complexity. Brawley said he had recently seen genomic data “that really gives me hope” that it will be possible to determine which men with prostate cancer are at high risk of progression and should be treated immediately and which can be managed by active surveillance. (See OT's recent coverage of the new Oncotype DX gene-based test for stratifying prostate cancer patients by risk, a test which is now available to clinicians.)