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结直肠癌的化学预防:准备好常规使用了吗?

Chemoprevention of colorectal cancer: ready for routine use?

作者信息

Arber Nadir, Levin Bernard

机构信息

Department of Cancer Prevention, Tel-Aviv Medical Center and Sackler School of Medicine, Tel Aviv University, 6 Weizmann St., Tel-Aviv 64239, Israel.

出版信息

Curr Top Med Chem. 2005;5(5):517-25. doi: 10.2174/1568026054201659.

Abstract

In the third millennium preventive medicine is becoming a corner stone in our concept of health. Colorectal cancer (CRC) prevention, in particular, has become an important goal for health providers, physicians and the general public. CRC fits the criteria of a disease suitable for chemopreventive interventions. It is a prevalent disease that is associated with considerable mortality and morbidity rates, with more than 1,000,000 new cases and 500,000 deaths expected, worldwide, in 2004. CRC has a natural history of transition from precursor to malignant lesion that spans, on average, 15-20 years, providing a window of opportunity for effective interventions and prevention. A pre-malignant precursor lesion (i.e., adenoma) usually precedes cancer, and helps to identify a subset of the population that is at increased risk of harbouring and developing cancer. Science and technology have evolved to a point where we are able to use our knowledge of cancer biology to identify individuals at risk and interrupt the process of malignant transformation at the level of the pre-cancerous lesion. Recent progress in molecular biology and pharmacology enhances the likelihood that cancer prevention will increasingly rely on chemoprevention. Chemoprevention, a new emerging science, means the use of agents to inhibit, delay or reverse carcinogenesis. Recent observations suggest a number of potential targets for chemoprevention. Many agents have potential benefit, but only modest chemopreventive efficacy in clinical trials. There is much evidence suggesting an inverse relationship between aspirin or NSAIDs consumption and CRC incidence and mortality. However, NSAID consumption is not problem-free, as 1997 data showed 107,000 hospitalisations and 16,500 deaths due to NSAIDs consumption in the US alone. Therefore, although chemoprevention of CRC is already possible, drugs that have more acceptable side-effect profiles than the currently available NSAIDs are required. COX-2-specific inhibitors, which have an improved safety profile, as compared to traditional NSAIDs that inhibit both the COX-1 and COX-2 enzymes, seem to be well suited drug candidates for CRC prevention. The inhibition of the growth of pre-cancerous and cancerous cells without affecting normal cells is the ultimate aim of cancer treatment and is of particular importance in chemoprevention studies, which may be long term in nature, involve healthy subjects and minimal toxicity. Cancer prevention is certain to be a significant focus of research and intervention in the coming years, propelled by the realization that we will be able to identify both individuals susceptible to specific cancers as well as the molecular targets that can alter or stop the carcinogenesis process. Pharmacology and genetics are collaborating to develop new chemoprevention agents designed to affect molecular targets linked to specific pre-malignant or predisposing conditions.

摘要

在第三个千年,预防医学正成为我们健康理念的基石。尤其是结直肠癌(CRC)的预防,已成为医疗服务提供者、医生和普通大众的重要目标。CRC符合适合化学预防干预的疾病标准。它是一种常见疾病,与相当高的死亡率和发病率相关,预计2004年全球将有超过100万新病例和50万例死亡。CRC有一个从前体病变转变为恶性病变的自然病程,平均持续15 - 20年,为有效干预和预防提供了机会之窗。癌前体病变(即腺瘤)通常先于癌症出现,有助于识别患癌风险增加的人群亚组。科学技术已经发展到我们能够利用癌症生物学知识识别高危个体并在癌前病变阶段阻断恶性转化过程的程度。分子生物学和药理学的最新进展增加了癌症预防将越来越依赖化学预防的可能性。化学预防是一门新兴科学,意味着使用药物抑制、延缓或逆转致癌作用。最近的观察结果提示了一些化学预防的潜在靶点。许多药物具有潜在益处,但在临床试验中化学预防效果有限。有大量证据表明阿司匹林或非甾体抗炎药(NSAIDs)的使用与CRC发病率和死亡率之间存在负相关。然而,服用NSAIDs并非毫无问题,因为1997年的数据显示仅在美国就有10.7万人因服用NSAIDs住院,1.65万人死亡。因此,尽管CRC的化学预防已经可行,但需要比目前可用的NSAIDs副作用更小的药物。与同时抑制COX - 1和COX - 2酶的传统NSAIDs相比,COX - 2特异性抑制剂具有更好的安全性,似乎是CRC预防的理想候选药物。在不影响正常细胞的情况下抑制癌前和癌细胞的生长是癌症治疗的最终目标,在化学预防研究中尤为重要,因为化学预防研究可能是长期的,涉及健康受试者且毒性最小。由于认识到我们将能够识别易患特定癌症的个体以及可改变或阻止致癌过程的分子靶点,癌症预防肯定会成为未来几年研究和干预的重要焦点。药理学和遗传学正在合作开发新的化学预防药物,旨在影响与特定癌前或易感状况相关联的分子靶点。

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