NCI Colorectal Cancer Group Outlines a Decade of Research Goals

BETHESDA, Md—A new National Cancer Institute report lays out a decade-long research plan aimed at answering major questions in colorectal cancer.

The report, Conquering Colorectal Cancer: A Blue Print for the Future, by NCI’s Colorectal Cancer Progress Review Group emerged from a meeting during which some 180 participants assessed what is known about colorectal cancer and made recommendations for improving the research effort against the disease.

The report consists of two sets of recommendations, one aimed at priority scientific questions and the other at overarching and resource issues.

Priority Scientific Questions

1. Biology. The report identified two high-priority areas for investigation: defining the biologic controls for the development of normal and abnormal colo-rectal epithelial development and defining the pathways of progression of colorectal neoplasia.

2. Etiology. The report emphasized three etiology research priorities. First, population-based epidemiologic studies that link genetic polymorphisms, diet and lifestyle variables, and endogenous factors with the molecular characteristics of colorectal cancer. Second, validation of early and intermediate biomarkers of exposure to environmental influences and genetic polymorphisms.

Third, the resequencing of single nucleotide polymorphism-containing genes involved in carcinogen or hormone metabolism, DNA repair, cell growth control, and immune response, and assessment of their functional polymorphisms in molecular epidemiologic studies in diverse ethnic populations using high-throughput genotyping methods.

3. Prevention. The report gave priority to defining pathways for nutritional and chemopreven-tive intervention; validating in human trials the usefulness of surrogate endpoint biomarkers identified in animal models; and initiating studies of combined lifestyle and chemopreventive interventions.

4. Early detection and diagnosis. The report gave priority status to three areas: research into strategies to effectively implement current recommended methods of early detection; rigorous clinical evaluation of promising markers and modalities before their widespread use; and development of new markers and modalities and improvement in current methods.

5. Treatment and prognosis. The report recommended fostering uniform delivery of accepted treatments and development of new regimens for locoregional disease. It also urged expediting new drug development by identifying intermediate endpoints and surrogate markers of response. Finally, it sought the comprehensive characterization of biologic features of both host and cancer to discover new indicators of prognosis.

6. Cancer control and survivorship. Research should include studies to identify the best standards of follow-up care after successful treatment, with a focus on which tests give the most information about important outcomes such as resectability, survival, cost, and psychosocial distress.

Researchers need to find ways to identify people at risk of adverse psychological distress, investigate whether psychosocial factors affect compliance, and assess the effectiveness of colorectal cancer screening, prevention, and treatment in the elderly and special populations.

Overarching and Resources Issues

The report’s recommendations with regard to “overarching and resources issues” include:

1. Genetics. Identify genes that predispose to colorectal cancer; determine how genetic screening and interventions affect morbidity, quality of life, and mortality in order to address counseling issues; and determine whether specific tumor genetic subtypes exist and how this knowledge can be used to improve drug development, intervention selection, and prognosis assessment.

2. Environment and lifestyle. Integrate observational screening and interven-tional approaches into future studies; improve assessment and characterization of lifestyle and environmental factors; and improve the biologic coherence of studies by assessing genetic and environmental factors in studies of the etiology and pathogenesis of colorectal cancer.

Monitoring Responses

3. Imaging. Apply functional and molecular imaging in screening, surveillance, and treatment strategies to enhance monitoring of chemopreventive and chemotherapeutic response; advance colorectal screening, staging, and surveillance by refining existing imaging technologies and developing new ones; and rapidly assess the benefits and risks of emerging imaging technologies.

4. Behavioral and health services. Develop models and methods that relate to the efficacy, effectiveness, and cost-effectiveness of intervention strategies, and characterize variations in patterns of colorectal cancer prevention, screening, diagnostic evaluation, and treatment.

Develop and evaluate strategies to improve access to screening, diagnostic evaluation, treatment, and clinical trials, and increase participation in clinical trials.

Provide greater interaction among the NCI, the FDA, pharmaceutical and biotechnology companies, physicians, and patient advocacy groups in order to “foster innovative approaches to drug discovery and development.”