BETHESDA, MarylandA 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
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
"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.
NCI listed four major objectives for improving prostate
Identify and validate new targets, novel therapeutic
agents, and optimal intervention approaches by disease stage in a clinical
Identify promising tools for enhancing and evaluating the
effectiveness of new therapies.
Identify and validate intermediate endpoints for clinical
trials of local and systemic therapies.
Strengthen the clinical trial infrastructure to increase
the number of rigorous clinical trials pivotal to developing and testing
The full report is available online at