New Strategies in Cancer Prevention and Treatment
This special report is based on an October 2003 grand rounds presentation by Dr. Michael B. Sporn. Dr. Sporn headed NCI's chemoprevention laboratory from its inception in 1978 until 1995. He is the current Oscar M. Cohn '34 Professor of Pharmacology and Medicine, Dartmouth Medical School and Eminent Scholar, NCI's Center for Cancer Research.
Development of modern chemotherapy for cancer originated in a unique translational environment at NIH more than 50 years ago. The opening of the Clinical Center in 1953 allowed Drs. Roy Hertz, Griff Ross, and Mort Lipsett to demonstrate convincingly - for the first time - that total cure of an advanced, potentially lethal cancer (choriocarcinoma) could be accomplished with chemotherapy.
This achievement led to the successful development at NCI of modern combination chemotherapy for leukemia and lymphoma. These were truly translational investigations. The animal studies that developed these new combination therapies were initiated on the NIH campus by Dr. Lloyd Law and colleagues and then translated for the first time into clinical reality by Drs. Tom Frei, Jay Freireich, and their Clinical Center colleagues. These collaborative studies are a model of the kind of cooperation between basic science and clinical application that is still needed to achieve NCI's goal of eliminating suffering and death due to cancer.
It has become clear, however, that the same paradigms for development and testing of cytotoxic agents that worked so well for the treatment of childhood leukemia will not suffice for the control of common malignancies that affect major organs - carcinoma of the lung, colon, pancreas, breast, and prostate - which collectively account for more than half of all cancer deaths.
The process through which leukemia develops is very different from the process by which these other carcinomas develop, explains Dr. Michael B. Sporn, who coined the term "chemoprevention" and is a pioneer in cancer prevention research. "We need to rethink our assumptions concerning control of carcinoma and place more emphasis on control of disease in its earliest, preinvasive stages," he says. "The disease itself is 'carcinogenesis,' an evolving process ultimately leading to the invasive state we call 'cancer.' This process is potentially more manageable in its earliest stages, before it becomes invasive. Most efforts to control cancer focus on treatment of end-stage, invasive, and metastatic disease, rather than on its prevention."Given this backdrop, the development of new prevention strategies is of paramount importance. To that end, research now is focusing on new molecular and cellular techniques for assessing individuals' cancer risk; identification of new molecular targets for prevention; and development of new drugs to suppress the carcinogenic process, either at its inception or in its initiated but preinvasive stages.
New diagnostics that take advantage of advances in proteomics and nanotechnology are needed to evaluate the extent of an individual's cancer risk and the efficacy of preventive drugs, adds Dr. Sporn. "Identifying individuals at risk for cancer as early as possible in the pathogenesis of their disease and then evaluating the efficacy of a preventive intervention as quickly as possible is essential if we are to have a real impact," he says.
Although such a preventive strategy holds great promise, it also will be exceedingly challenging. Scientifically speaking, explains Dr. Sporn, this strategy is intrinsically more complex than the classical clinical approach of waiting for relatively advanced disease to manifest itself and starting treatments that can be more easily evaluated because the patient is already symptomatic.
"The complexities of this new approach to prevention provide NCI with an opportunity to play a leadership role in a national effort to prevent cancer," he says. "NCI has the unique ability to make the long-term commitments to prevention. It has unique resources, in terms of the scientific and clinical talents of its staff, as well as its world-class laboratories and new clinical facilities. In such a national effort, NCI will act as a bridge whereby basic scientific knowledge can be applied in a translational manner to reach an ultimate goal."