As War On Cancer Hits 25-Year Mark, Scientists See Progress, Challenges

It's 25 years and counting since President Richard Nixon signed the National Cancer Act on Dec. 23, 1971, marking the United States' official declaration of war on cancer. The act provided funding to establish medical centers dedicated to clinical research and cancer treatment under the auspices of the National Cancer Institute (NCI). Yet, after an estimated $28 billion spent to find cures and better treatments for the dreaded disease, the war is far from over. Most scientists note the tremendous strides made in treating -- and even curing -- some cancers -- particularly childhood leukemias and Hodgkin's disease. They point to new breakthroughs in understanding the molecular and genetic processes of the cancer cell. In addition, they note, patients now live longer and have a better quality of life. But critics invariably point to one inexorable fact: Cancer is on the rise and no abatement is in sight. The major killers -- lung, breast, colon, and prostate cancer -- remain so, and some -- namely, melanoma -- are increasing in incidence. At best, many researchers contend, slow, steady progress is being made. Counterbalancing this pessimism are some hard numbers showing reason for optimism. For the first time since the 1930s -- when mortality figures were first kept -- cancer death rates are dropping. A paper published last month supports the notion that prevention is paying off (P. Cole, B. Rodu, Cancer, 78:2045-8, 1996). Epidemiologist Philip Cole and colleague Brad Rodu at the University of Alabama, Birmingham, found that age-adjusted cancer mortality in the U.S. has been falling steadily since 1990, and fell by nearly 3 percent from 1991 to 1995. The largest turnaround was in lung cancer, which dropped nearly 3.9 percent. Cole attributes the drop to decades of anti-smoking efforts and improvements in medical care, including treatment and early diagnosis. The authors also predict that the decline will continue for decades. NO POETIC LICENSE: Oncologist Samuel Hellman warns that hyping cancer research breakthroughs sends the wrong message. The report, announced on November 14 at an NCI news conference by director Richard Klausner, received worldwide attention. Yet some worry that the wrong message is getting out. Oncologist Samuel Hellman, A.N. Pritzker Distinguished Service Professor at the University of Chicago, warns against "colleagues and the media hyping major breakthroughs in cancer research." Though the recent figures on cancer mortality appear promising, he notes, the war is far from won. "[It] hasn't really been a war -- it's been more like a skirmish," contends Fran Visco, president of the National Breast Cancer Coalition in Washington, D.C. "It hasn't been funded appropriately and hasn't been put on the country's agenda." However, she notes, things are beginning to change as funds are preserved, and more scientists and members of the public sit at the table and map out the U.S.'s research goals. From her perspective, "they need to focus on research that has a direct impact and is translatable to the patient." Vincent T. DeVita, Jr., NCI director from 1980 to 1988, remembers when NCI carried out half of all NIH's molecular biology research. Despite a call from some scientists to spend more money on research into treatments such as chemotherapy, NCI put its money into basic research. Now, he's "gratified how the investment has paid off," and that current NCI director Klausner -- who was unavailable for comment for this article -- is continuing the institute's commitment. "The mandate of the [National Cancer] act was to support basic research and to reduce incidence and mortality," DeVita says. "We've done that." He points out that in judging progress of the war on cancer, "improvements in morbidity, such as a reduction in nausea and vomiting, are overlooked. Women undergoing mastectomy are no longer subjected to terribly disfiguring surgeries. Surgical techniques have improved, and fewer patients than ever lose limbs from bone cancer. The best is yet to come." DeVita concedes that he was "one of the critics when they declared war" in 1971. He thought the institute was just throwing money at the problem without any direction. "I thought it was crazy. . . . But money does buy ideas. How? You put the best scientists to work and they generate ideas." Yet, the initial goal of curing cancer by 1976 was unrealistic, he maintains. "In retrospect, the time frame of curing cancer by the [U.S.] bicentennial was shortsighted; we didn't have the technology." He contends that researchers who pushed the war on cancer at the beginning were oversold on chemotherapy as a cure. 'NAIVE IDEAS': In the beginning, researchers had simplistic views on the causes of cancer, according to Bruce Chabner. "We had naive ideas of what we could do with the available technology," adds Bruce Chabner, chief of hematology-oncology and clinical director of the Massachusetts General Hospital Cancer Center. "We had simplistic ideas of cancer -- we really didn't know what caused it. We had little understanding of the biological difference between tumor and normal tissue." Despite all the research, he notes, gaps in knowledge remain. "We still don't know how to translate knowledge about genetic defects into effective drugs." Indeed, Nobel laureate Joshua Lederberg, Raymond and Beverly Sackler Foundation Scholar at Rockefeller University, spelled out the challenge 25 years ago in the Washington Post (J. Lederberg, Feb. 14, 1971, page C2). "We simply do not have the basic knowledge to do more than gain time with many cancers after they have reached a certain state of development. . . . The greatest promise, of course, comes from the great leaps in basic biological knowledge of the last decade, many of them in the related areas of DNA and viruses." However, DeVita contends that new and different approaches will be needed to take the next steps in applying new molecular knowledge of the cancer cell. Scientists are learning how normal cells turn cancerous, how they communicate and spread, and how they resist drugs and radiation. "The machinery in getting from here to there is old," he comments. "To take the molecular information from research to clinical trials will need a completely different approach. The great excitement from the molecular biology revolution will lie fallow because it has no effective outlet. [Using] the findings about the cell cycle and the drugs' effects on the cancer cell will take a different set of parameters, and perhaps different methods of drug testing and clinical trials. We need to make sure the machinery works more effectively." NEW PRIORITIES NEEDED: Epidemiologist John Bailar contends that the U.S. has spent enough on the search for cures. Not everyone regards the drop in death rates as a definitive victory in the war on cancer. Critics such as University of Chicago epidemiologist John C. Bailar III say that the efforts have not been enough, and that after a quarter-century of trying to find cures, perhaps it's time to adjust the nation's priorities. "I think it's foolish to think that someday we'll find cures [for cancer]," Bailar asserts. "I think we cannot base national strategy on that kind of hope." He believes more efforts should be put into finding the causes, rather than cures, of cancer. Prevention should take top priority as well, he maintains. While at McGill University in Montreal in 1986, Bailar coauthored a controversial paper that outlined how cancer rates were rising and why the United States was losing the war (J.C. Bailar, E.M. Smith, New England Journal of Medicine, 314:1226-32). Bailar, who is now director of health studies at Chicago, says he has heard enough talk about the U.S.'s war on cancer and about the potential for making measurable advances in reducing cancer by the turn of the century. By his estimate, the new numbers show overall U.S. age-adjusted cancer mortality flattening out, not dropping. Age adjustment takes into account the growing aging U.S. population and the drop in deaths from other diseases such as heart disease and stroke. Bailar cites several cures that never panned out: "We've heard about cancer viruses, then it was immunology, designer drugs -- remember interferon? It washed out despite the publicity." Interferon, a natural substance, burst onto the cancer scene in the 1970s as a highly touted "cure." To date, it has yet to live up to its billing, though it is effective in treating some rare cancers. "Will molecular genetics do it?," he wonders. "I don't know. I think it's dumb to assume it will." He is quick to note that scientists have learned a huge amount about the molecular and genetic underpinnings of cancer, and of how it begins and how it spreads. The other benefit from the war is in general knowledge about medicine. The cancer research effort in virology and immunology has been instrumental in the first major breakthroughs in AIDS, Bailar contends. He comments that DeVita and others are looking at the "victories" in the war on cancer differently. "In terms of knowledge of the genetics and the molecular biology of the cancer, it's true. But I'm looking downstream. I've heard these arguments since 1956 that we have to just wait, that we're learning what to do. I'm still waiting." Bailar advocates a change of NCI dollar allotment to favor by 2 to 1 an investment in prevention research over treatment. He estimates the current ratio is 4 to 1 in favor of research on treatment. OLD ARGUMENTS: There will always be disagreements on whether to spend money on prevention or treatments, says Robert Young. Such spending arguments are nothing new to Robert Young, president of the Fox Chase Cancer Center in Philadelphia. "An age-old argument of the cancer research community is how to distribute finite resources," he says. "Many say we should concentrate money on treatments while others say we should focus on prevention. There has to be a continuing search for better disease treatments, because we'll always have people with cancer. We have to figure out how to treat them more effectively. We need better early detection. Take breast cancer. Even if every woman was able to have mammograms in a timely manner, best estimates show that we'd prevent maybe 30 percent [of breast cancers]. What about the other 70 percent?" Since 1970, prevention studies-particularly those regarding smoking cessation and control -- have made a huge impact, notes Young. "We've made some modest progress in the treatment of disease, found some causes of some cancers, rid the workplace of cancer-causing substances. . . . It's true that we are not any closer to curing lung cancer. But in the 1970s and since, prevention has paid off -- identifying the causes of cancers, improving treatments of advanced disease in a handful of cancers, adjuvant treatment, early diagnosis for breast and cervix -- all have contributed to this decline in nationwide cancer mortality." ANOTHER PERSPECTIVE: From a minority point of view, M.D. Anderson’s Lovell Jones contends, "we’re losing the war." Despite the encouraging news, the war on cancer is far from over for minorities, many claim. Lovell Jones, cofounder of the Intercultural Cancer Council (ICC), a broad-based group representing community and cancer- advocacy organizations, questions NCI's commitment to minorities and the medically underserved. From the minority point of view, says Jones, who is director of experimental gynecology/endocrinology at M.D. Anderson Cancer Center in Houston, "we're losing the war on cancer." While the reported five-year cancer death rate for African Americans dropped more than that for white Americans-5.6 percent for African Americans compared with only 1.7 percent for whites-cancer rates are still about 40 percent higher in the former group. He believes that NCI's office of minority affairs, headed by Otis Brawley, will begin to properly address the lack of minority participation in clinical trials. The ICC urged Congress to ask the Institute of Medicine (IoM) to look at cancer research efforts among minorities and the medically underserved to determine why the rates of incidence and mortality continue to rise in minorities at a greater rate than in other populations. On October 1, Congress passed legislation calling for an IoM study of cancer and minority research at NIH, covering "relative share of NIH resources allocated to cancers disproportionately afflicting minorities and the medically underserved . . . minority scientists' involvement in decision making on research priorities . . . whether NIH has a sufficient overview of cancer among minorities to prioritize a research agenda dealing with multiple contributing factors such as genetics, environment, behavioral factors, including diet and smoking, socioeconomic factors, and access to health care." "I think with the passage of this legislation, it is proactively beginning to address these problems," Jones notes. He worries that if Congress views the falling cancer mortality rates as proof that the war on cancer has been won, it may argue that NCI doesn't need major funding increases. Minority numbers, he notes, are climbing in all areas. He's hoping that the IoM study will "recommend that since the numbers are dropping in white populations, now is the time to focus resources in prevention and education, and treatment research on the minority and medically underserved." Despite the optimism resulting from the recently announced downswing in cancer mortality figures, many challenges remain. Massachusetts General Hospital's Chabner comments that "progress has been tremendous in understanding the biology of cancer, [but] we're a long way from getting a complete understanding of cancer, and we're a long way from implementing the new knowledge in a useful way. "We haven't developed effective strategies for vaccines or genetic screening -- we can only do that for a few genes -- and we don't have effective means of identifying high-risk individuals," says Chabner. "The task of the next generation of researchers is to apply this to make a measurable impact on mortality. We haven't really made efficient use of this new knowledge yet -- that's the major challenge of the next 30, 40 years." 'A SKIRMISH': Lack of funding and policy has kept the war on cancer from achieving its goals, says activist Fran Visco. National Cancer Advisory Board (NCAB) chairwoman Barbara Rimer sees daunting challenges ahead as well. As an NCI external advisory body, NCAB oversees grant application reviews and offers advice on cancer research programs. To Rimer, a professor of community and family medicine and director of cancer prevention, detection, and control research at Duke University Cancer Center, these include revising the guidelines for cancer centers; strengthening the role of prevention in NCI research; finding solutions to the problems caused by the impact of managed care on cancer institutions, including how to pay for clinical trials; and accelerating discovery in basic, clinical, and population-based research. Rimer contends that "we need much more attention to prevention. In view of the fact that more than one-half of all cancers are potentially preventable by changes in behavior, we must start to bring the spending portfolio into line with the opportunities for preventing cancer. That means, above all, significantly more attention to developing better ways to prevent smoking among youth and to help smokers quit for good. We should be investing in the next generation of pharmacologic aids for smoking cessation as well as better chemoprevention strategies. "We will also need to develop better educational programs to prepare the next generation of prevention scientists," she adds. "We need scientists who can work in the new scientific paradigms, who are trained in cancer genetics, statistics, epidemiology, [and] outcomes research as well as other areas, such as behavioral science, clinical medicine, and molecular biology." The National Breast Cancer Coalition's Visco agrees: "We'll only make inroads on cancer if we focus on prevention. We don't know for sure what areas to focus on, nor if it will work," she says, echoing Bailar's comments. "However, we know that we need to prevent kids from smoking, and the FDA [Food and Drug Administration] should regulate access. But we still don't know what causes breast cancer, and we need to put more money into prevention."

As War On Cancer Hits 25-Year Mark, Scientists See Progress, Challenges

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