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结直肠癌预防的分子标志物与靶点

Molecular markers and targets for colorectal cancer prevention.

作者信息

Janakiram Naveena B, Rao Chinthalapally V

机构信息

Department of Medicine, Hem-Onc Section, OU Cancer Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

出版信息

Acta Pharmacol Sin. 2008 Jan;29(1):1-20. doi: 10.1111/j.1745-7254.2008.00742.x.

Abstract

Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from promoting/ developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the biological and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarker in biomolecular pathway are elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.

摘要

结直肠癌是全球第三大常见癌症。如果在早期阶段被检测到,治疗往往可能导致治愈。由于预防胜于治疗,流行病学研究表明,保持健康的饮食通常可以预防癌症的发生/发展。评估新药和新设备时的一个重要考虑因素是确定一种产品是否能有效治疗目标疾病。有相当数量的生物标志物正在进入临床试验,还有少数正在等待临床前疗效和安全性结果以便进入临床试验。研究人员在修改试验设计、确定合适的对照人群、从生物学和分析角度验证生物标志物检测方法以及将生物标志物数据用作决策指南等方面面临挑战。尽管遵循了所有指南,但许多大型临床试验的结果却令人失望。为避免这些失望情况,需要在合适的动物模型中评估生物标志物及其靶向药物的毒性和疗效。本综述的重点是结直肠癌中一些潜在的分子靶点及其生物标志物。还讨论了生物标志物/替代终点的优势和局限性。阐明了肿瘤细胞中涉及的各种途径以及针对生物分子途径中改变的分子生物标志物的特定药物。综述了新兴的新平台siRNAs和miRNAs技术在结直肠癌治疗中的重要性。

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