Current Address: Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20850, USA.
Center for Chemoprevention and Drug Development, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Int J Mol Sci. 2018 Aug 8;19(8):2332. doi: 10.3390/ijms19082332.
Substantial efforts are underway for prevention of early stages or recurrence of colorectal cancers (CRC) or new polyp formation by chemoprevention strategies. Several epidemiological, clinical and preclinical studies to date have supported the chemopreventive potentials of several targeted drug classes including non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, naproxen, sulindac, celecoxib, and licofelone), statins and other natural agents-both individually, and in combinations. Most preclinical trials although were efficacious, only few agents entered clinical trials and have been proven to be potential chemopreventive agents for colon cancer. However, there are limitations for these agents that hinder their approval by the food and drug administration for chemoprevention use in high-risk individuals and in patients with early stages of CRC. In this review, we update the recent advancement in pre-clinical and clinical development of selected anti-inflammatory agents (aspirin, naproxen, sulindac, celecoxib, and licofelone) and their combinations for further development as novel colon cancer chemopreventive drugs. We provide further new perspectives from this old research, and insights into precision medicine strategies to overcome unwanted side-effects and overcoming strategies for colon cancer chemoprevention.
目前正在进行大量工作,通过化学预防策略来预防结直肠癌(CRC)的早期阶段或复发或新息肉形成。迄今为止,几项流行病学、临床和临床前研究支持了包括非甾体抗炎药(NSAIDs)(阿司匹林、萘普生、舒林酸、塞来昔布和利福昔酮)、他汀类药物和其他天然药物在内的几类靶向药物的化学预防潜力——单独使用和联合使用。虽然大多数临床前试验都有效,但只有少数药物进入临床试验,并已被证明是结肠癌的潜在化学预防药物。然而,这些药物存在一些限制,阻碍了它们被食品和药物管理局批准用于高危人群和 CRC 早期患者的化学预防用途。在这篇综述中,我们更新了选定抗炎药物(阿司匹林、萘普生、舒林酸、塞来昔布和利福昔酮)及其组合在临床前和临床开发方面的最新进展,以进一步开发为新型结肠癌化学预防药物。我们从这项旧研究中提供了新的观点,并深入了解了精准医学策略,以克服不良副作用和克服结肠癌化学预防的策略。