Patient-Derived Xenograft Models of Non-Small Cell Lung Cancer and Their Potential Utility in Personalized Medicine.
Patient-Derived Xenograft Models of Non-Small Cell Lung Cancer and Their Potential Utility in Personalized Medicine.
复制标题
患者衍生的非小细胞肺癌异种移植模型及其在个性化医疗中的潜在用途。
DOI：
10.3389/fonc.2017.00002
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发表时间：
2017
影响因子：
4.7
通讯作者：
Pine SR
中科院分区：
文献类型：
--
作者：
Morgan KM;Riedlinger GM;Rosenfeld J;Ganesan S;Pine SR
传统的癌症治疗的临床前研究依赖于使用已建立的人类细胞系，这些细胞系已适应在实验室中生长，因此可能偏离它们所代表的癌症。随着癌症药物开发的重点从非特异性细胞毒性药物转向合理设计的分子靶向治疗或免疫治疗，需要在临床试验中对治疗活性和反应具有预测价值的更好的模型。最近，免疫缺陷小鼠品系的多样性和可及性极大地提高了许多肿瘤类型（包括非小细胞肺癌（NSCLC））的患者源性异种移植（PDX）模型的生产和应用。结合下一代测序，NSCLC PDX小鼠模型为药物开发和研究靶向治疗提供了一个令人兴奋的工具，同时利用患者样本，希望最终有助于临床决策。在这里，我们描述了由我们和其他人建立的NSCLC PDX小鼠模型，它们反映亲代肿瘤组织形态学特征的能力，以及克隆选择和进化对维持低传代PDX中与供体组织相比基因组完整性的影响。我们还提出了关于PDX和人性化PDX模型在预测患者对治疗反应方面的实际应用的重要问题，并提出了解决这些问题的建议。一旦合作和标准化异种移植和数据管理方法建立起来，NSCLC PDX小鼠模型就有可能成为一种普遍和宝贵的临床前工具，指导临床试验和标准治疗决策。
Traditional preclinical studies of cancer therapeutics have relied on the use of established human cell lines that have been adapted to grow in the laboratory and, therefore, may deviate from the cancer they were meant to represent. With the emphasis of cancer drug development shifting from non-specific cytotoxic agents to rationally designed molecularly targeted therapies or immunotherapy comes the need for better models with predictive value regarding therapeutic activity and response in clinical trials. Recently, the diversity and accessibility of immunodeficient mouse strains has greatly enhanced the production and utility of patient-derived xenograft (PDX) models for many tumor types, including non-small cell lung cancer (NSCLC). Combined with next-generation sequencing, NSCLC PDX mouse models offer an exciting tool for drug development and for studying targeted therapies while utilizing patient samples with the hope of eventually aiding in clinical decision-making. Here, we describe NSCLC PDX mouse models generated by us and others, their ability to reflect the parental tumors’ histomorphological characteristics, as well as the effect of clonal selection and evolution on maintaining genomic integrity in low-passage PDXs compared to the donor tissue. We also raise vital questions regarding the practical utility of PDX and humanized PDX models in predicting patient response to therapy and make recommendations for addressing those questions. Once collaborations and standardized xenotransplantation and data management methods are established, NSCLC PDX mouse models have the potential to be universal and invaluable as a preclinical tool that guides clinical trials and standard therapeutic decisions.