An Integrative Approach to Precision Cancer Medicine Using Patient-Derived Xenografts.
An Integrative Approach to Precision Cancer Medicine Using Patient-Derived Xenografts.
复制标题
DOI：
10.14348/molcells.2016.2350
复制
发表时间：
2016-02
影响因子：
3.8
通讯作者：
Park H
中科院分区：
文献类型：
--
作者：
Cho SY;Kang W;Han JY;Min S;Kang J;Lee A;Kwon JY;Lee C;Park H
癌症是由癌基因和肿瘤抑制基因的不同基因组改变引起的异质性疾病。尽管最近在高通量测序技术和靶向治疗的发展方面取得了进展，但由于临床研究的高损耗率，新型癌症药物的开发受到限制。通过将患者肿瘤转移到免疫缺陷小鼠中建立的患者来源的异种移植物（PDX）通过整合临床数据、基因组图谱和药物反应性数据来确定精确的靶向疗法，从而作为共同临床试验的平台。PDX模型保留了患者肿瘤的许多关键特征，包括组织学、基因组特征、细胞异质性和药物反应性。这些模型也可以应用于药物反应性和个性化药物选择的生物标志物的开发。这篇综述总结了我们目前在这一领域的知识，包括方法学方面，在药物开发中的应用，挑战和限制，以及精确癌症医学的利用。
Cancer is a heterogeneous disease caused by diverse genomic alterations in oncogenes and tumor suppressor genes. Despite recent advances in high-throughput sequencing technologies and development of targeted therapies, novel cancer drug development is limited due to the high attrition rate from clinical studies. Patient-derived xenografts (PDX), which are established by the transfer of patient tumors into immunodeficient mice, serve as a platform for co-clinical trials by enabling the integration of clinical data, genomic profiles, and drug responsiveness data to determine precisely targeted therapies. PDX models retain many of the key characteristics of patients’ tumors including histology, genomic signature, cellular heterogeneity, and drug responsiveness. These models can also be applied to the development of biomarkers for drug responsiveness and personalized drug selection. This review summarizes our current knowledge of this field, including methodologic aspects, applications in drug development, challenges and limitations, and utilization for precision cancer medicine.