BETHESDA, Maryland—A 6-year prostate cancer research plan released by the National Institutes of Health (NIH) contains a detailed outline of the National Cancer Institute’s (NCI) future strategy for dealing with the disease, which includes a shift in the standard treatment model from seek-and-destroy to target-and-control.
"This new paradigm has been referred to as a ‘regulatory model’ of cancer, viewing cancer as a maladaptive, evolving process with cancer cells differing from normal cells as a consequence of critical genetic changes leading to dysregulation of growth," the report said.
Under the regulatory model, standard therapies would be combined with additional therapies to control the growth and spread of remaining cancer cells by targeting the multiple molecular pathways involved in dysregulation, the report said.
The 48-page report, titled "Prostate Cancer Research Plan FY 2003-FY2008," resulted from a request by the Senate Committee on Appropriations. The committee asked NIH to address concerns that research on the disease "has not kept pace with scientific opportunities and the proportion of the male population afflicted with the disease." An estimated 189,000 US men will be diagnosed with prostate cancer in 2002, and 30,200 will die from it.
Although NCI is the lead federal agency investigating prostate cancer, the new plan also describes research efforts related to the disease at seven other NIH units: the National Institute of Diabetes and Digestive and Kidney Diseases, National Human Genome Research Institute, National Center for Research Resources, National Institute of Environmental and Health Sciences, National Institute on Aging, National Institute of Nursing Research, and National Institute of Mental Health.
The NIH report identifies goals, objectives, and strategies for seven critical areas of prostate cancer research: biology, progression, and metastasis; etiology and prevention; early detection, diagnosis, and prognosis; treatment; cancer control, survivorship, and outcomes; laboratory and preclinical models; and resource and capacity building.
"Prostate cancer researchers must also have the necessary funding to enable the finest quality research to strive," the report said.
One key aim of the NCI program is to identify the molecular pathways that cause prostate cancer, and its progression and metastasis. This will require reliable experimental models that mimic the behavior of the human disease, and basic research to identify genes important in prostate cancer," the report said.
"An equally important area of research is to understand the roles of the micro- and macroenvironment of a tumor in the development and progression of prostate cancer," it added. "Such research includes efforts to identify the biological changes influenced by biological, physical, and psychosocial factors."
Two other biological goals are to understand the molecular mechanisms behind androgen-independent prostate cancer and to decipher the relationship between the clinical course and the biological features of the disease.
Prevention
"Increasing our understanding of causes is essential to the development of effective prevention methods," the report said. "Further research is also needed to determine what causes some prostate cancers to become particularly aggressive while others remain relatively harmless. Identifying risk factors and determining how they contribute not only to onset of the disease but also to progression will provide the foundation for effective prevention strategies."
NCI also plans to use the knowledge gained about the molecular and cellular biology of prostate cancer to develop better ways to detect and diagnose premalignant and malignant tumors and to better predict disease progression and patient response to therapy.
It cited, as an example, the recent discovery of the protein thymosin beta 15, which stimulates cell motility and the invasion of surrounding tissues, and occurs in elevated amounts in prostate cancer cells. The protein is now in a clinical trial to determine its potential as a prognostic test for the disease.
Better Treatments
NCI listed four major objectives for improving prostate cancer treatment:
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Identify and validate new targets, novel therapeutic agents, and optimal intervention approaches by disease stage in a clinical setting.
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Identify promising tools for enhancing and evaluating the effectiveness of new therapies.
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Identify and validate intermediate endpoints for clinical trials of local and systemic therapies.
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Strengthen the clinical trial infrastructure to increase the number of rigorous clinical trials pivotal to developing and testing novel therapeutics.
The full report is available online at http://searchosp1.nci.nih.gov/index.html.
