Colorectal cancer models for novel drug discovery.
Colorectal cancer models for novel drug discovery.
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DOI：
10.1517/17460441.2015.1079618
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发表时间：
2015
影响因子：
6.3
通讯作者：
Roper J
中科院分区：
文献类型：
--
作者：
Golovko D;Kedrin D;Yilmaz ÖH;Roper J
尽管筛查率提高和靶向治疗的进展，结直肠癌（CRC）仍然是癌症相关死亡的第三大原因。概括人类疾病关键特征的CRC模型对于开发新的有效治疗方法至关重要。经典的CRC建模方法，如人类细胞系和异种移植小鼠，虽然适用于许多应用，但具有显著的局限性。最近开发的体外和体内模型克服了这些缺陷中的一些，因此可以用来更好地模拟CRC的机制和转化研究。作者回顾了体外细胞培养的模型，并描述了研究正常和恶性肠道的类器官培养的进展。他们还讨论了经典异种移植模型的关键特征，并描述了体内CRC研究的其他方法，包括患者来源的异种移植，致癌物诱导，原位移植和转基因小鼠模型。我们还描述了转移性CRC的小鼠模型。没有一个模型是CRC药物发现的最佳模型。基因工程模型克服了异种移植模型的许多局限性。三维类器官可以有效地来源于正常和恶性组织，用于大规模的体外和体内（移植）研究，因此是CRC药物发现的重大进展。
Despite increased screening rates and advances in targeted therapy, colorectal cancer (CRC) remains the third leading cause of cancer-related mortality. CRC models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. Classic methods of modeling CRC such as human cell lines and xenograft mice, while useful for many applications, carry significant limitations. Recently developed in vitro and in vivo models overcome some of these deficiencies and thus can be utilized to better model CRC for mechanistic and translational research. The authors review established models of in vitro cell culture and describe advances in organoid culture for studying normal and malignant intestine. They also discuss key features of classic xenograft models and describe other approaches for in vivo CRC research, including patient-derived xenograft, carcinogen-induced, orthotopic transplantation, and transgenic mouse models. We also describe mouse models of metastatic CRC. No single model is optimal for drug discovery in CRC. Genetically engineered models overcome many limitations of xenograft models. Three-dimensional organoids can be efficiently derived from both normal and malignant tissue for large-scale in vitro and in vivo (transplantation) studies, and are thus a significant advance in CRC drug discovery.