人源肿瘤异种移植模型（PDX）在精准肿瘤医学中的研究进展

癌症是由于物理、化学、病毒等致癌因子导致的原癌基因和抑癌基因突变从而引发的一系列异质性疾病的统称。尽管近年来高通量测序技术与靶向治疗取得了突破性的进展，但是临床转化研究的高失败率使得抗肿瘤药物的创新发展十分有限。人源肿瘤异种移植模型（patient-derived xenograft model，PDX模型）是指直接将病人的新鲜肿瘤组织移植到免疫缺陷小鼠上，依靠小鼠提供的环境生长的一种异种移植模型。这种模型保留了原代肿瘤的基质异质性、组织学特性、分子多样性以及微环境，为临床前药效的个性化筛选评估以及生物标志物的鉴定提供了有效的研发资源。PDX模型结合临床数据，基因组图谱以及药效数据可以增加药物特异性，应用于肿瘤患者个体化治疗，提高临床治疗成功率。本文就PDX模型研究进展进行综述，包括其在肿瘤新疗法中的应用、挑战性与局限性、以及在精准肿瘤医学中的应用前景。

Research progress of patient-derived xenografts in precision cancer medicine

Cancer is a group of 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) models are generated by implanting sectioned patient tumor fragments into immunodeficient mice. PDX models retain many of the key characteristics of patients'' tumors including histology, genomic signature, cellular heterogeneity, and drug responsiveness. These models cannot only 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, but 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.