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推动3D肿瘤模型在癌症药物研发流程中的广泛应用。

Toward the Broad Adoption of 3D Tumor Models in the Cancer Drug Pipeline.

作者信息

Cox Megan C, Reese Laura M, Bickford Lissett R, Verbridge Scott S

机构信息

School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, Virginia 24061, United States.

出版信息

ACS Biomater Sci Eng. 2015 Oct 12;1(10):877-894. doi: 10.1021/acsbiomaterials.5b00172. Epub 2015 Sep 11.

Abstract

Despite a cost of approximately $1 billion to develop a new cancer drug, about 90% of drugs that enter clinical trials fail. A tremendous opportunity exists to streamline the drug selection and testing process, and innovative approaches promise to reduce the burdensome cost of health care for those suffering from cancer. There is great potential for 3D models of human tumors to complement more traditional testing methods; however, the shift from 2D to 3D assays at early stages of the drug discovery and development process is far from widely accepted. 3D platforms range from simple tumor spheroids to more complex microfluidic hydrogels that better mimic the tumor microenvironment. While several companies have developed and patented advanced high-throughput 3D platforms for drug screening, their cost and complexity have limited their adoption as an industry standard. In this review, we will highlight the various tumor platforms that have been developed, emphasizing the approaches that have successfully led to commercial products. We will then consider potential directions toward more relevant tumor models, advantages of the adoption of such platforms within the drug development and screening process, and new opportunities in personalized medicine that such platforms will uniquely enable.

摘要

尽管研发一种新型抗癌药物的成本约为10亿美元,但进入临床试验的药物约有90%会失败。简化药物筛选和测试过程存在巨大机遇,创新方法有望减轻癌症患者沉重的医疗费用负担。人类肿瘤的3D模型有很大潜力补充更传统的测试方法;然而,在药物发现和开发过程的早期阶段从二维检测转向三维检测远未被广泛接受。3D平台范围从简单的肿瘤球体到更复杂的微流控水凝胶,后者能更好地模拟肿瘤微环境。虽然几家公司已经开发出先进的用于药物筛选的高通量3D平台并取得专利,但其成本和复杂性限制了它们作为行业标准被采用。在本综述中,我们将重点介绍已开发的各种肿瘤平台,强调那些已成功带来商业产品的方法。然后,我们将考虑朝着更相关肿瘤模型发展的潜在方向、在药物开发和筛选过程中采用此类平台的优势,以及此类平台将独特实现的个性化医疗中的新机遇。

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