The Conquest of Cancer

For the first time since records have been kept, death rates from cancer in the United States have dropped--by some 2.6 percent between 1991 and 1995. These figures are encouraging when compared with cancer mortality rates recorded during the previous decade (1981-1990), which actually increased.It is likely these successes result from several factors, including more effective methods of treating cancers; better, more widely used techniques to diagnose cancers early; and progress in the prevention of some cancers. Moreover, we have entered a period of unprecedented biological discovery. Perhaps most importantly, we have harnessed the power of new technologies to identify genes involved in the development of cancers and forever change how we think about these diseases.Surgery, chemotherapy, and radiation therapy remain the mainstays of cancer treatment and continue to be improved. But today investigators are developing targeted cancer treatments, many of which home in on cancer cells while leaving healthy cells relatively unscathed. A variety of new treatments are being developed. Among these approaches are agents that can induce cancer cells to differentiate and arrest the tumors; agents that block the effect of specific oncogenes; gene therapy to increase immune response to cancer; agents that inhibit the development of blood vessels to tumors, leading to tumor cell death; synthetic "vaccines" that specifically induce immune responses to cancers such as prostate, melanoma, colon, and breast; and small molecules that inhibit the abnormal signal pathway leading to uncontrolled cell growth.Perhaps the most exciting area of cancer research is genetics. Today we know that cancers develop when certain genes that normally govern cell growth are altered, leading to the rampant growth that is the hallmark of these diseases. Of the estimated 80,000 to 100,000 genes in each cell of the human body, more than 100 have thus far been identified as "cancer" genes, which, when altered or mutated, can increase the risk of cancer.Researchers have set out to identify every major human gene that can predispose an individual to cancer. This new knowledge will enhance our understanding of how our genes interact with substances in the environment to cause cancer. It is estimated that about 90 percent of all cancers are due to somatic mutations, and only 10 percent due to inherited "cancer" gene mutations. The transformation from a normal to a cancer cell generally requires an accumulation of changes in the structure of an estimated four to six "cancer" genes occurring over a lifetime. These changes may result from exposure to various environmental hazards, many of which have not been definitely identified and some of which have--e.g., radiation, ultraviolet rays, cigarette smoke.Genetic discoveries have already given us diagnostic tests to identify people with an increased risk for certain cancers. Discoveries of abnormalities in DNA, RNA, and proteins associated with cancer are providing prognostic tests that are becoming important tools for therapeutic decisions. Even more exciting is the promise that gene discovery will provide new targets for the development of better treatments.The identification of persons predisposed to cancer raises a host of medical, ethical, social, policy, and financial issues. Our present ability to identify a person at risk is not matched by our ability to prevent the cancer to which that person may be susceptible. Further, the privacy of such sensitive information must be considered; there is the potential for discrimination in seeking employment, health insurance--even marriage. How we deal with these issues will determine, to a large extent, our ability to apply our increasing understanding of the role of genetics to the effective prevention and early detection of cancers.A critical component in efforts to control and cure cancer in the 21st century will be how well we communicate our ever-expanding knowledge to both physicians and the public. "Best" cancer therapy involves multiple therapeutic modalities; that is, surgery and/or chemotherapy, and/or other new approaches to diagnosis, prognosis, and treatment. More than ever, doctors will have to be continually updated on recent advances.At Memorial Sloan-Kettering Cancer Center, we have developed a Disease Management System. This is an approach to cancer care that integrates patient care services; provides standard treatment practices for more than 90 different cancers in detail to reduce the variability of care; and provides clinical, financial, and patient-oriented quality of life outcomes.The entire professional staff, physicians, and nurses are members of one or more disease-oriented teams. Each team is responsible for developing the best-practice clinical pathways and clinical research and monitoring these pathways and investigational protocols to maintain the highest possible quality and exploit effective advances in any aspect of care. The pathways are reviewed periodically and appropriately altered based on outcome data and new advances. Our physicians access this information through customized computer software. As for the public, a most important step is for people to take advantage of the technology currently available to detect cancers in their earliest and most curable stages.Because cancers result from interactions between our genetic makeup and our environment, it is not realistic to expect to eliminate these diseases as we have eliminated smallpox and polio. But there is no doubt that the application of our increasing understanding of the nature of cancer will lead to promising new approaches to prevention and care that will markedly reduce the burden of this disease for the individual and for society.Paul A. Marks, M.D., is president and chief executive officer of Memorial Sloan-Kettering Cancer Center, New York. Web address: www.mskcc.org (See also Notebook, page 31)

The Conquest of Cancer

We have harnessed the power of new technologies to identify genes involved in the development of cancers and forever change how we think about these diseases.

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