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Progress in clinical chemoprevention
G J Kelloff1, E T Hawk, J E Karp
1Division of Cancer Prevention and Control, Chemoprevention Branch, National Cancer Institute, Bethesda, MD 20852, USA.
Abstract:
Chemoprevention has four goals: (1) inhibition of carcinogens, (2) logical intervention for persons at genetic risk for cancer, (3) treatment of precancerous lesions, and (4) confirmation and translation of leads from dietary epidemiology into intervention strategies. The National Cancer Institute has described a multidisciplinary, cancer science-based program for chemopreventive drug development that addresses these objectives, and has collaborated with the US Food and Drug Administration to provide consensus guidance for applying this approach. A critical component is the identification and characterization of intermediate biomarkers of cancer and their validation as surrogate end points for cancer incidence in clinical chemoprevention trials. More than 40 agents in the program are currently on the clinical development path (preclinical toxicology and phase I clinical safety studies or phase II/III efficacy trials), with the major effort in phase II studies to identify and characterize intermediate biomarkers. The continually advancing knowledge of molecular and tissue-based carcinogenesis mechanisms will provide leads to new chemopreventive agents with increased specificity for carcinogenesis-related activities and, hence, reduced toxicity by virtue of minimal effects on normal cell and tissue functions. Results from the Human Genome Project will help identify and evaluate the potential for chemopreventive intervention in cohorts at genetic risk and will provide specific target lesions for intervention strategies.
Insights
Chemoprevention aims to inhibit carcinogens and treat precancerous lesions. The National Cancer Institute
Area of Science:
- Oncology
- Preventive Medicine
- Molecular Biology
Background:
- Chemoprevention targets four key areas: carcinogen inhibition, genetic risk intervention, precancerous lesion treatment, and translating dietary findings into strategies.
- The National Cancer Institute (NCI) has developed a multidisciplinary, science-based program for chemopreventive drug development.
- Collaboration with the US Food and Drug Administration (FDA) provides guidance for implementing chemoprevention strategies.
Purpose of the Study:
- To outline the goals and multidisciplinary approach of the NCI's chemopreventive drug development program.
- To emphasize the importance of identifying and validating intermediate biomarkers as surrogate endpoints in clinical trials.
- To highlight the role of advancing molecular carcinogenesis knowledge and the Human Genome Project in future chemoprevention.
Main Methods:
- Development of a multidisciplinary, cancer science-based program for drug discovery.
- Collaboration with regulatory bodies (FDA) for consensus guidance.
- Focus on identifying and characterizing intermediate biomarkers in Phase II clinical studies.
- Utilizing knowledge from molecular carcinogenesis and the Human Genome Project.
Main Results:
- Over 40 agents are in clinical development, with a significant focus on Phase II studies for biomarker characterization.
- Advancing understanding of carcinogenesis mechanisms is leading to more specific and less toxic chemopreventive agents.
- The Human Genome Project is expected to aid in identifying at-risk populations and specific targets for intervention.
Conclusions:
- Chemoprevention is a multifaceted strategy with a robust drug development program guided by scientific advancement.
- Biomarker validation is crucial for the success of clinical chemoprevention trials.
- Future chemoprevention will benefit from molecular insights and genetic risk assessments.