文章：

预防癌症的非甾体抗炎药：前景、危险和药物遗传学

Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics

原文发布日期：2006-02-01

DOI: 10.1038/nrc1801

类型: Review Article

开放获取: 否

要点：

1. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective chemopreventive agents against colorectal neoplasia.
2. NSAID use is associated with a reduced risk of several other types of malignancies, but randomized controlled trials for primary or secondary prevention are still needed.
3. A key mechanism for NSAID efficacy is cyclooxygenase (COX) inhibition and reduced production of prostaglandins.
4. COX2-specific inhibitors (COXibs) might be less toxic to the gastrointestinal tract than NSAIDs that target both COX1 and COX2. However, cardiovascular toxicity associated with COXibs raises concerns.
5. Inherited genetic factors can explain some inter-individual differences in NSAID metabolism and prostaglandin synthesis.
6. Initial epidemiological studies indicate that only in a genetically defined subset of the population will NSAIDs prevent colorectal neoplasia, which suggests pharmacogenetic effects.
7. Pharmacogenetic investigations are expected to help establish the individual risk–benefit ratio for NSAID use and therefore allow tailoring of chemoprevention.
8. In general, a multi-agent, multi-targeted approach to chemoprevention is to be recommended. However, NSAIDs are effective as single agents because they work early in carcinogenesis across multiple pathways.

要点翻译：

1. 非甾体抗炎药（NSAIDs）是预防结直肠肿瘤的有效化学预防药物。
2. NSAIDs的使用与降低多种其他类型恶性肿瘤的风险相关，但仍需进行用于一级或二级预防的随机对照试验。
3. NSAIDs疗效的关键机制是抑制环氧化酶（COX）和减少前列腺素的产生。
4. 与同时靶向COX1和COX2的NSAIDs相比，特异性COX2抑制剂（COXibs）可能对胃肠道的毒性较小。然而，COXibs相关的心血管毒性引起了担忧。
5. 遗传因素可以解释NSAIDs代谢和前列腺素合成中的部分个体差异。
6. 初步流行病学研究表明，NSAIDs仅在遗传定义的特定人群亚组中能够预防结直肠肿瘤，这提示了药物遗传学效应。
7. 药物遗传学研究有望帮助确定NSAIDs使用的个体风险-获益比，从而实现化学预防的个体化定制。
8. 总体而言，推荐采用多药物、多靶点的化学预防策略。然而，NSAIDs作为单一药物也有效，因为它们在致癌过程的早期阶段通过多种途径发挥作用。

英文摘要：

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) show indisputable promise as chemopreventive agents. Possible targets include cancers of the colon, stomach, breast and lung. However, recent studies raise concern about potential cardiovascular toxicity associated with the use of NSAIDs that specifically target the enzyme cyclooxygenase 2. These findings, and others that show that inherited genetic characteristics might determine preventive success, argue for new strategies that are tailored to individual medical history and genetic make-up.

摘要翻译： 

阿司匹林及其他非甾体抗炎药（NSAIDs）作为化学预防药物的前景无可争议。其潜在靶点包括结直肠癌、胃癌、乳腺癌和肺癌。然而，最新研究提示，特异性抑制环氧合酶-2（COX-2）的NSAIDs可能带来心血管毒性风险。这些发现，连同遗传特征可能决定预防效果的证据，均支持应依据个体病史和基因构成制定新的精准策略。

原文链接：

Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics