Related Experiment Videos
Progress in cancer chemoprevention
G J Kelloff1, J A Crowell, V E Steele
1National Cancer Institute, Division of Cancer Prevention, Bethesda, Maryland 20892, USA. kelloffg@dcpcepn.nci.nih.gov
Abstract:
More than 40 promising agents and agent combinations are being evaluated clinically as chemopreventive drugs for major cancer targets. A few have been in vanguard, large-scale intervention trials--for example, the studies of tamoxifen and fenretinide in breast, 13-cis-retinoic acid in head and neck, vitamin E and selenium in prostate, and calcium in colon. These and other agents are currently in phase II chemoprevention trials to establish the scope of their chemopreventive efficacy and to develop intermediate biomarkers as surrogate end points for cancer incidence in future studies. In this group are fenretinide, 2-difluoromethylornithine, and oltipraz. Nonsteroidal anti-inflammatories (NSAID) are also in this group because of their colon cancer chemopreventive effects in clinical intervention, epidemiological, and animal studies. New agents are continually considered for development as chemopreventive drugs. Preventive strategies with antiandrogens are evolving for prostate cancer. Anti-inflammatories that selectively inhibit inducible cyclooxygenase (COX)-2 are being investigated in colon as alternatives to the NSAID, which inhibit both COX-1 and COX-2 and derive their toxicity from COX-1 inhibition. Newer retinoids with reduced toxicity, increased efficacy, or both (e.g., 9-cis-retinoic acid) are being investigated. Promising chemopreventive drugs are also being developed from dietary substances (e.g., green and black tea polyphenols, soy isoflavones, curcumin, phenethyl isothiocyanate, sulforaphane, lycopene, indole-3-carbinol, perillyl alcohol). Basic and translational research necessary to progress in chemopreventive agent development includes, for example, (1) molecular and genomic biomarkers that can be used for risk assessment and as surrogate end points in clinical studies, (2) animal carcinogenesis models that mimic human disease (including transgenic and gene knockout mice), and (3) novel agent treatment regimens (e.g., local delivery to cancer targets, agent combinations, and pharmacodynamically guided dosing).
Insights
Chemopreventive drugs are in clinical trials for various cancers, with research focusing on novel agents and biomarkers. This includes dietary compounds and targeted anti-inflammatories to improve cancer prevention strategies.
Area of Science:
- Oncology
- Pharmacology
- Preventive Medicine
Background:
- Over 40 chemopreventive agents are under clinical evaluation for major cancer types.
- Large-scale trials are investigating agents like tamoxifen and fenretinide for breast cancer, and NSAIDs for colon cancer.
- Research is exploring new retinoids, dietary compounds, and selective COX-2 inhibitors.
Purpose of the Study:
- To review the current landscape of chemopreventive drug development.
- To highlight agents in phase II trials for efficacy and biomarker development.
- To discuss ongoing research in novel agents and preventive strategies.
Main Methods:
- Clinical trials (Phase II and large-scale intervention studies).
- Epidemiological and animal studies for agent validation.
- Basic and translational research for biomarker and model development.
Main Results:
- Numerous agents show promise, with some in advanced trials.
- Biomarkers are being developed as surrogate endpoints for cancer incidence.
- Newer agents, including dietary substances and selective COX-2 inhibitors, are under investigation.
Conclusions:
- Chemoprevention research is advancing with diverse agents and strategies.
- Development of molecular biomarkers and improved models is crucial for progress.
- Combination therapies and targeted delivery show potential for future cancer prevention.