Department of Oncology & Neurosciences, "G. D'Annunzio" University, Chieti-Pescara, Italy.
Eur Rev Med Pharmacol Sci. 2010 Apr;14(4):285-91.
Chemoprevention of gastrointestinal tumors uses natural or synthetic agents to arrest, retard or reverse the carcinogenesis process. The prospect of prevention is clearly appealing, especially for colorectal cancer (CRC), that represents the second most common cause of cancer-related death in the Western world. Aspirin is the best studied chemopreventive agent for CRC, with randomized trials demonstrating its efficacy in reducing recurrence of colorectal adenomas in higher risk patients. Optimal chemoprevention requires long-term use and high dose of aspirin that may increase the risk of gastrointestinal bleeding. Other nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors also reduce the incidence of colonic adenomas, but they are associated with gastrointestinal harms and important cardiovascular events, respectively. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent for CRC. The usefulness of folic acid, calcium, and vitamin D awaits further evaluation. Interestingly, combining different agents may maximize effectiveness while limiting drug toxicity. Although many agents have shown positive results in the field of chemoprevention, it cannot yet be accepted as standard medical practice for CRC. In the present review we discuss the most promising agents in CRC chemoprevention, together with their potential mechanisms of action in tumor inhibition.
胃肠道肿瘤的化学预防使用天然或合成药物来阻止、延缓或逆转癌变过程。预防的前景显然很有吸引力,特别是对于结直肠癌(CRC),它是西方世界癌症相关死亡的第二大主要原因。阿司匹林是研究最多的 CRC 化学预防药物,随机试验表明其在降低高危患者结直肠腺瘤复发方面的疗效。最佳的化学预防需要长期使用和高剂量的阿司匹林,这可能会增加胃肠道出血的风险。其他非甾体抗炎药和选择性环氧化酶-2 抑制剂也可降低结肠腺瘤的发生率,但它们分别与胃肠道损害和重要的心血管事件相关。此外,累积的流行病学和观察性数据表明,激素可能作为 CRC 的化学保护剂发挥作用。叶酸、钙和维生素 D 的作用尚待进一步评估。有趣的是,联合使用不同的药物可能会最大限度地提高疗效,同时限制药物毒性。尽管许多药物在化学预防领域显示出积极的结果,但它还不能被接受为 CRC 的标准医学实践。在本综述中,我们讨论了 CRC 化学预防中最有前途的药物,以及它们在肿瘤抑制中的潜在作用机制。