Publications and Presentations
Extraordinary Opportunities for Early Cancer Detection and Risk Assessment Research
Conclusions
An integrated, multidisciplinary approach to early detection and risk assessment is likely to be more successful in cancer prevention than any other approach. For example, the linkage of early detection research to active screening trials or to prevention studies would accelerate the validation of biomarkers. Both molecular markers and interventions may be evaluated in the same study or trial, a potential saving in time and resources. Additionally, linking an effective intervention to the screening process would improve subject participation and maximize efficiency of the total process. The CBRG has and will continue to initiate collaborations with various programs in NCI and other federal agencies (such as the Food and Drug Administration, Centers for Disease Control and Prevention, and the National Institute of Standards and Technology). CBRG will also seek joint initiatives with industry, using the Cooperative Research and Development Agreement mechanism, to accelerate the development of new generations of molecular markers for early cancer detection and risk assessment.
In the short term, our focus is on those biomarkers which have been proven biologically relevant and have high levels of reproducibility and accuracy. Markers such as p53 mutations, ras mutations, proliferation markers, telomerase, and microsatellite instability, for example, must move beyond their current status as interesting laboratory observations with small numbers of samples to their application population-based validation studies. It will be necessary to organize the burgeoning number of candidate markers and to categorize the relevant markers for each tumor site. Additionally, new generations of gene expression markers are likely to be discovered from the NCI Cancer Genome Anatomy Projects (CGAP). The CBRG will continue to interact and collaborate with the CGAP investigators. It should be noted, however, that prior to their integration into population screening, molecular markers must be validated ultimately in controlled clinical trials.
In the long term, the major research initiatives addressing the development of molecular markers need to combine basic science discoveries concerning early events in cancer with new detection technologies. Potentially useful modalities should then be evaluated using clinically well-defined, histologically normal, preneoplastic and neoplastic lesions, collected with ancillary demographic and epidemiological data. These studies need to focus on the identification, characterization, and validation of molecular markers in high-risk individuals and accompanying demographic and epidemiologic data that could lead to the successful development of early detection markers for high-risk subgroups drawn from the population. The translational research studies needed to achieve these goals will require attention to several critical areas: 1) tissue acquisition; 2) resource development; 3) technology development; and 4) major research initiatives. An additional important resource necessary for developing and validating molecular markers are model systems. These would involve promoting and supporting: 1) cell culture systems which reflect the epithelial cell types, 2) whole organ culture systems which mimic the structure, cellular interaction, and growth or whole organs, and 3) animal models where the development of epithelial tumors is frequent and can be followed in various stages.
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