Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested with humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including three-dimensional (3D) cell culture models. Three-dimensional tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of physiologically relevant drug diffusion, paracrine signalling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.
在临床试验之前，候选肿瘤药物的临床前测试通过体外和体内平台进行评估。对于体内测试，动物模型被用于评估候选药物的毒性和疗效。然而，动物模型往往表现出较差的转化结果，因为许多通过临床前测试的药物在人体试验中失败，其中肿瘤药物的接受率尤其低。《FDA现代化法案2.0》推动了替代性临床前测试技术的发展，为使用更高复杂度的体外模型（包括三维细胞培养模型）替代体内测试提供了机会。三维组织培养通过结合生理相关的药物扩散、旁分泌信号传导、细胞表型和血管化，更接近地模拟肿瘤微环境，从而解决了二维培养的许多缺点，能更好地模拟人体原生组织。本综述将讨论三维细胞培养的常见形式，包括细胞球体、类器官、芯片器官和三维生物打印组织。将介绍它们的优势和局限性，旨在探讨这些三维模型如何准确模拟人体组织并作为动物测试的替代方案。随着这些平台在复杂性、可靠性和转化预测性方面的持续改进，三维培养平台在临床前药物开发中的应用预计将加速推进。
Preclinical Testing Techniques: Paving the Way for New Oncology Screening Approaches
肿瘤(癌症)患者之家