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Selecting targets for cancer prevention: where do we go from here?

Nature Reviews Cancer volume 6, pages 867–874 (2006)Cite this article

Key Points

  • The selection of agents for cancer prevention requires a thorough understanding of the potential efficacy and toxicities that are associated with specific agents.

  • Evidence of effectiveness for prevention comes from a knowledge of mechanisms, in vitro and animal in vivo experimental data, epidemiological case–control and cohort studies, and data from clinical trials (both early-phase cancer prevention trials and secondary endpoint analysis of trials performed for other indications).

  • Risk–benefit considerations are crucial to the choice of agents for cancer prevention. The greater the risk of cancer, the greater the toxicity that is acceptable. There is a great need to improve risk-assessment tools to identify those individuals with the highest cancer risk who stand to gain the most benefit from preventive interventions.

  • Understanding the molecular mechanisms and the temporal sequence of events that result in carcinogenesis are crucial to the choice of agents and the design of prevention trials. Interventions need to target specific abnormalities when these abnormalities are crucial to cancer development.

  • New clinical trial designs are needed for efficient cancer preventive drug evaluation. Nesting 'prevention endpoints' into cancer treatment trials provides opportunities for the simultaneous development of agents for prevention and treatment if the toxicity profile of the agent is benign enough to warrant prevention applications.

Abstract

Given the lack of progress in curing metastatic epithelial cancers, there is intense interest in, and a sound scientific rationale for, pursuing strategies to prevent cancer. However, although several clinical trials have shown efficacy in cancer prevention, few have resulted in changes to medical practice, and some trials have even shown harm. Recent experiences with serious side effects identified in cancer prevention trials underscore the need to re-evaluate our approach to clinical chemopreventive drug development, and to establish a framework for agent selection for future trials.

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Figure 1: Timing and targets for prevention.

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Acknowledgements

The author would like to thank R. Lubet for helpful discussions and comments.

Author information

Authors and Affiliations

  1. Division of Cancer Prevention, Lung and Upper Aerodigestive Cancer Research Group, National Cancer Institute, 6130 Executive Boulevard, Room 2132, Bethesda, 20892, Maryland, USA

    Eva Szabo

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  1. Eva Szabo
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DATABASES

National Cancer Institute

breast cancer

cervical cancer

colorectal cancer

CML

lung cancer

oral cancer

prostate cancer

skin cancer

Glossary

Familial adenomatous polyposis

A genetic disorder that is characterized by an increased predisposition to colorectal cancer, associated with germ-line mutations of the APC gene.

Hypertension

Persistently high arterial blood pressure. This condition is considered a risk factor for the development of heart disease, peripheral vascular disease, stroke and kidney disease.

Case–control study

A study in which the risk factors of people with a disease are compared with those without the same disease.

Cohort study

A clinical trial in which a cohort with a particular attribute (such as smokers or recipients of a drug) is followed prospectively and compared for some outcomes (such as cancer or cure) with another cohort not possessing the attribute.

Pharmacodynamic

The effects on the biochemistry of the body that result from treatment with a drug or combination of drugs.

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Szabo, E. Selecting targets for cancer prevention: where do we go from here?. Nat Rev Cancer 6, 867–874 (2006). https://doi.org/10.1038/nrc2008

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