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  • Review Article
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Chemoprevention of lung carcinogenesis in addicted smokers and ex-smokers

Nature Reviews Cancer volume 9, pages 476–488 (2009)Cite this article

Key Points

  • Lung cancer kills more than 3,000 people every day, and most of this toll is due to cigarette smoking. Although tobacco control is clearly the most desirable way to prevent lung cancer, cigarette smoking is addictive and, despite considerable success to date, there are still more than 1 billion smokers in the world who, along with ex-smokers, are at high risk for lung cancer. Chemoprevention of lung carcinogenesis is one way forward in the control of this devastating disease.

  • In considering chemoprevention, it is crucial that we focus on treating lung carcinogenesis, not lung cancer. The disease process is carcinogenesis.

  • Lung carcinogenesis is caused by numerous carcinogens in cigarette smoke, along with tumour promoters, co-carcinogens, toxicants and inflammatory agents. In devising chemoprevention strategies, these agents should be our targets. Targeting a single pathway in lung carcinogenesis is not likely to be successful.

  • Because there are numerous carcinogenic and toxic constituents of tobacco smoke, we need to develop a mixture of chemopreventive agents to counteract them. This mixture should be developed from the ground up, using animal models to demonstrate efficacy without appreciable toxicity.

  • Well-established animal models are available for evaluating chemopreventive efficacy against lung carcinogenesis. The most commonly used model by far is the carcinogen-treated A/J mouse, which develops similar adenocarcinoma to that seen in humans.

  • Many agents have shown chemopreventive efficacy against lung carcinogenesis in animal models. Examples include phenethyl isothiocyanate, indole-3-carbinol, myo-inositol, green and black tea and its constituents, silibinin, glucocorticoids, difluoromethylornithine, oleanane and ursane triterpenoids, non-steroidal anti-inflammatory drugs, farnesyltransferase inhibitors, organoselenium compounds and others. Some mixtures of these agents also demonstrate efficacy.

  • There have been no successful lung carcinogenesis clinical trials. Current trials include examinations of some of the agents listed above, but no mixtures.

  • In chemoprevention of lung carcinogenesis, we must target current smokers, smokers transitioning to quitting and ex-smokers. Although cessation is clearly the best way to decrease the probability of the onset of lung cancer, most smokers cannot quit, even after many tries. It would be unethical not to offer these people effective agents.

Abstract

Chemoprevention of lung carcinogenesis is one approach to controlling the epidemic of lung cancer caused by cigarette smoking. The target for chemoprevention should be the activities of the multiple carcinogens, toxicants, co-carcinogens, tumour promoters and inflammatory compounds in cigarette smoke. At present there are many agents, both synthetic and naturally occurring, that prevent lung tumour development in well-established animal models. It seems likely that logically constructed mixtures of these agents, developed from the ground up, will be necessary for the prevention of lung carcinogenesis.

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Figure 1: A design for evaluating chemopreventive agents against lung tumorigenesis in A/J mice.
Figure 2: Structures of diverse inhibitors of lung carcinogenesis.
Figure 3: Chemoprevention of lung cancer in a mouse model using a mixture of preventive agents.

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Acknowledgements

The authors' research on chemoprevention of lung carcinogenesis is supported in part by grants number CA-81301, CA-102502, CA-128801 and DA-13333 from the US National Institutes of Health and grant number RP-00-138 from the American Cancer Society. We thank B. Carlson for outstanding assistance in the preparation of this manuscript.

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  1. Masonic Cancer Center, University of Minnesota, Mayo Mail Code 806, 420 Delaware Street South East, Minneapolis, 55455, Minnesota, USA

    Stephen S. Hecht, Fekadu Kassie & Dorothy K. Hatsukami

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DATABASES

National Cancer Institute Drug Dictionary 

atorvastatin

budesonide

celecoxib

dexamethasone

difluoromethylornithine

myo-inositol

PEITC

polyphenon E

rapamycin

Sulindac

Targretin

FURTHER INFORMATION

Stephen S. Hecht's homepage

National Cancer Institute Clinical Trials

Glossary

Chronic obstructive pulmonary disease

(COPD). An umbrella term used to describe chronic bronchitis, emphysema or both. COPD is usually caused by smoking, and symptoms include coughing and breathlessness.

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Hecht, S., Kassie, F. & Hatsukami, D. Chemoprevention of lung carcinogenesis in addicted smokers and ex-smokers. Nat Rev Cancer 9, 476–488 (2009). https://doi.org/10.1038/nrc2674

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