Today, cancer is the second leading cause of death in the United States, with more than 500,000 men, women, and children succumbing to the disease each year. The idea, then, that we can eliminate the suffering and death due to cancer in the United States by the year 2015 may appear impractical, if not irrational and impossible. It seems inconceivable that in the first part of the 21st century every patient could survive cancer. Doubt can be attributed to awareness of the biologic complexity of cancer and seeing the pace of clinical progress through the prism of the 20th century.
However, in 2002, when setting the goal of eliminating the suffering and death due to cancer, the National Cancer Institute (NCI) envisioned a future in cancer research and care that would be radically different from the past, and be the fruition of the cancer enterprise made possible by the National Cancer Act of 1971. Because of progress thus far, there are more than 10 million cancer survivors today, and two out of every three people diagnosed with cancer will be alive 5 years following diagnosis. Because of prospects for future progress, it is within our grasp to prevent more cancers from occurring, to detect others earlier and eliminate them more effectively and safely, and to modulate the behavior of other cancers, so that patients will be able to live with, and not die from, the disease.
For those willing to embrace the possibility of such a future, the question remains: How can such a goal be accomplished, and how can it be achieved in such a short time? This paper will describe the rationale for the goal and present a way forward that, with proper leadership and resources, will lead to this lifesaving objective. To achieve a clear vision of this path, one must scrutinize the past and acquire a new vantage point from which to see the future. It requires us to no longer consider cancer as an event clouded in mystery, but as a process with defined and knowable mechanisms that operate in a distinct manner over time, resulting in ample opportunities and sufficient time for intervention (Figure 1). It requires us to consider the pace and trajectory of future progress, not as an extrapolation of past experience, but as a new reality born of a metamorphosis in medical science and technology.
The pathway to preempting the outcome of the cancer process is not a defined roadmap; rather, it is a way forward, with sequential steps and parallel paths toward a defined goal. Inherent in the way forward is the assumption that paths will, at times, converge and technology will accelerate the speed of progress, so that over the next decade, passing milestones on the journey will be astounding compared with past progress. The key to seeing what is possible is to view the journey from the perspective of the evolution in scientific discovery. That is, the perspective of a metamorphosis from a macroscopic and microscopic view of cancer to a molecular one.
Macroscopic and Microscopic Traditions of the Past
The history of the quest to conquer cancer has been nested in a model of health and health care that has addressed disease from a phenotypic perspective. Our knowledge of cancer is derived from our observation of the manifestations of the disease. For thousands of years, this phenotypic perspective dominated the practice of medicine based on what we could learn using our five senses. Medical education focused on creating a sound foundation of physical diagnosis through observation, auscultation, percussion, and palpation. What we could feel and see defined the taxonomy of disease. Cancers were named for the organ in which they originated.
Approximately 100 years ago, we moved from this macroscopic view to a microscopic perspective. A revolutionary change of seeing cancer cells under a microscope refined our characterization of cancer and allowed us to infer more about its behavior, but again, an inference derived from what we could see or observe of cell size and shape. Certainly this was significant progress; and when our vision was further sharpened by x-ray techniques and laboratory studies, our ability to observe phenotypic expression of disease was dramatically enhanced. But in fact, the fundamental paradigm remained unchanged, and detection and diagnosis were completely discontinuous with therapeutic intervention.
Observing the anatomic and morphologic expression of cancer provided no insight into what the ideal intervention would be, and treatment required a separate and empiric set of strategies based on ablation or eradication of the phenotypic expression of the disease. Throughout most of the 20th century, our efforts at tumor ablation by surgery, radiation, and chemotherapy were largely empiric; progress was measured by expanding the limits of ablation and reducing the morbidity and mortality associated with therapy. But progress did occur.
At the beginning of the 20th century, cancer was a uniformly fatal disease. By the end of the 20th century, there were examples of enormous advances in some cancers, such as childhood leukemia and testicular cancer with chemotherapy, and dramatic improvements in the results of surgery and radiation therapy in early prostate and breast cancer. But in therapeutic strategies that required an understanding of mechanisms, such as immunotherapy, results were disappointing. Many cancers did not respond to chemotherapy regimens that were dramatically effective in other cancers, with no apparent explanation. The most significant benefit seemed to emanate from the major impact of a prevention strategy that was based on an observation of tobacco's mechanistic causation of lung cancer.
But along this journey of an empiric approach to a macroscopic and microscopic perspective of cancer, an important transformation occurred. With the signing of the National Cancer Act of 1971, the NCI obtained both the authorities and the appropriations to begin a focused and directed effort to "understand" cancer. It was the catalyst that was necessary to rapidly and radically accelerate the emergence of the new field of molecular biology. With the discovery of DNA by Watson and Crick in 1953 and the post-World War II explosion in science and technologies that followed our understanding of the nature of matter and energy, the world was poised to begin the exploration of life processes in the cell.
The most egregious disruption of the nominal processes of proliferation and differentiationand the most readily available for studywas the cancer cell. Cancer led the revolution in molecular and cell biology in the last quarter of the 20th century, and in the last decade of the century, we crossed the threshold into the molecular era. This was now more than a transformation. It was a metamorphosis in which the future in oncology will be no more like the past than a butterfly is like a caterpillar.