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吸烟成瘾者和戒烟者肺癌发生的化学预防

Chemoprevention of lung carcinogenesis in addicted smokers and ex-smokers

原文发布日期：2009-07-01

DOI: 10.1038/nrc2674

类型: Review Article

开放获取: 否

要点：

要点翻译：

英文摘要：

摘要翻译：

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文章：

吸烟成瘾者和戒烟者肺癌发生的化学预防

Chemoprevention of lung carcinogenesis in addicted smokers and ex-smokers

原文发布日期：2009-07-01

DOI: 10.1038/nrc2674

类型: Review Article

开放获取: 否

要点：

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.

要点翻译：

肺癌每日导致逾3000人死亡，其中绝大多数归因于吸烟。虽然烟草控制显然是预防肺癌最理想的方式，但吸烟具有成瘾性，尽管目前已取得显著成效，全球仍有超过10亿吸烟者及其曾经的吸烟者群体面临极高的肺癌风险。肺癌致癌过程的化学预防是控制这一致命疾病的重要方向。
在考虑化学预防时，关键要着眼于治疗肺癌发生过程而非已形成的肺癌。这一疾病进程本质上是致癌作用。
肺癌发生是由香烟烟雾中大量致癌物连同促癌剂、辅助致癌物、毒性物质和炎症介质共同引发的。制定化学预防策略时，这些因素应成为我们的干预目标。仅针对肺癌发生过程中的单一通路不太可能取得成功。
鉴于烟草烟雾含有众多致癌和毒性成分，我们需要开发复合型化学预防剂来中和其危害。这种复合制剂应当从基础研究起步，通过动物模型验证其有效性且不产生明显毒性。
目前已有成熟的动物模型用于评估肺癌化学预防效果，其中应用最广泛的是致癌物处理的A/J小鼠模型，该模型可诱发与人类相似的腺癌。
多种制剂在动物模型中显示出对肺癌发生的化学预防效果，例如异硫氰酸苯乙酯、吲哚-3-甲醇、肌醇、绿茶和红茶及其成分、水飞蓟宾、糖皮质激素、二氟甲基鸟氨酸、齐墩果烷型和乌索烷型三萜类化合物、非甾体抗炎药、法尼基转移酶抑制剂、有机硒化合物等。这些制剂的某些组合方案也显示出协同功效。
目前尚未有成功的肺癌化学预防临床试验。现行试验主要针对上述部分单一制剂，尚未涉及复合制剂研究。
在肺癌化学预防领域，我们必须聚焦当前吸烟者、正在戒烟过渡期者及既往吸烟者。尽管戒烟无疑是降低肺癌发生概率的最佳途径，但大多数吸烟者即使经过多次尝试仍难以成功戒烟。若不为这些人群提供有效预防制剂，将违背医学伦理原则。

英文摘要：

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.