For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab.
一个多世纪以来,早期研究者致力于在实验室环境中研究生物有机体,由此催生了体外与体内模型系统。近年来,患者来源的癌症模型(PDMCs)已成为临床前癌症模型的前沿领域,甚至作为功能性精准医疗项目的一部分进入临床实践。由美国国立卫生研究院国家癌症研究所癌症生物学部门支持的PDMC联盟,致力于探究调控各类PDMC生物学行为的基本原理,特别是其对癌症治疗等干扰因素的反应机制。基于联盟成员机构的集体经验,我们通过系列专题案例,深入探讨了体外与体内建立的PDMC模型,重点关注关键癌症模型开发与维护的实际问题。尽管每种模型都可能提供有价值的见解,但模型选择应以研究问题为导向。同时,充分认识各模型的内在局限性至关重要。本文旨在通过具体案例阐明各类模型的优势与局限。PDMC模型的持续进步及新型模型系统的发展,将推动我们更深入地理解人类生物学,并优化实验室环境下人类病理学研究体系。