大规模日本患者来源异种移植(J-PDX)文库的特征描述。

Characterization of the large-scale Japanese patient-derived xenograft (J-PDX) library.

机构信息

Division of Molecular Pharmacology, National Cancer Center Research Institute, Chuo-ku, Japan.

Department of Head and Neck Medical Oncology, National Cancer Center Hospital, Chuo-ku, Japan.

出版信息

Cancer Sci. 2021 Jun;112(6):2454-2466. doi: 10.1111/cas.14899.

Abstract

The use of patient-derived xenografts (PDXs) has recently attracted attention as a drug discovery platform with a high predictive clinical efficacy and a preserved tumor heterogeneity. Given the racial differences in genetic variations, it would be desirable to establish a PDX library from Japanese cancer patients on a large scale. We thus tried to construct the Japanese PDX (J-PDX) library with a detailed clinical information for further clinical utilization. Between August 2018 and May 2020, a total of 1126 cancer specimens from 1079 patients were obtained at the National Cancer Center Hospital and National Cancer Center Hospital East, Japan, and were immediately transplanted to immunodeficient mice at the National Cancer Center Research Institute. A total of 298 cross-cancer PDXs were successfully established. The time to engraftment varied greatly by cancer subtypes, especially in the first passage. The engraftment rate was strongly affected by the clinical stage and survival time of the original patients. Approximately 1 year was needed from tumor collection to the time when coclinical trials were conducted to test the clinical utility. The 1-year survival rates of the patients who were involved in establishing the PDX differed significantly, from 95.6% for colorectal cancer to 56.3% for lung cancer. The J-PDX library consisting of a wide range of cancer subtypes has been successfully established as a platform for drug discovery and development in Japan. When conducting coclinical trials, it is necessary to consider the target cancer type, stage, and engraftment rate in light of this report.

摘要

患者来源异种移植(PDXs)最近作为一种具有高临床疗效预测性和保留肿瘤异质性的药物发现平台引起了关注。鉴于遗传变异的种族差异,最好在日本建立一个包含大量癌症患者的 PDX 文库。因此,我们试图构建具有详细临床信息的日本 PDX(J-PDX)文库,以便进一步临床应用。2018 年 8 月至 2020 年 5 月,我们在日本国家癌症中心医院和日本国家癌症中心医院东部共获得了 1079 名患者的 1126 个癌症标本,并立即在国家癌症中心研究所将其移植到免疫缺陷小鼠体内。总共成功建立了 298 个跨癌 PDX。肿瘤植入的时间因癌症亚型而异,尤其是在第一阶段。原始患者的临床分期和生存时间强烈影响植入率。从肿瘤采集到进行 coclinical 试验以测试临床实用性,大约需要 1 年时间。参与建立 PDX 的患者的 1 年生存率差异很大,从结直肠癌的 95.6%到肺癌的 56.3%。该 J-PDX 文库包含广泛的癌症亚型,已成功建立为日本药物发现和开发的平台。在进行 coclinical 试验时,需要根据本报告考虑目标癌症类型、分期和植入率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87df/8177812/7bbcf06244a0/CAS-112-2454-g001.jpg

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