Rapid screening for individualized chemotherapy optimization of colorectal cancer: A novel conditional reprogramming technology-based functional diagnostic assay.
Rapid screening for individualized chemotherapy optimization of colorectal cancer: A novel conditional reprogramming technology-based functional diagnostic assay.
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结直肠癌个体化化疗优化的快速筛选：一种新的基于条件重编程技术的功能诊断分析。
DOI：
10.1016/j.tranon.2020.100935
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发表时间：
2021-01
影响因子：
5
通讯作者：
Wu A
中科院分区：
文献类型：
--
作者：
Li Y;Guo D;Zhang Y;Wang L;Sun T;Li Z;Zhang X;Wang S;Chen Y;Wu A
建立了一种新的体外肿瘤模型，称为新型条件性重编程（novel conditional reprogrammed，简称i-CR）。在2-3周内完成个性化药物测试。达到100%的灵敏度，85.7%的特异性，91.7%的阳性预测值，和100%的阴性预测值。i-CR指导了1例无法手术的转移瘤患者转为根治性手术。体外患者肿瘤模型，如患者源性类器官（PDO）和条件重编程（CR）细胞培养，对于转化研究和临床前药物测试非常重要。在这项研究中，我们提出了一个个性化的药物敏感性测试的晚期，潜在的可手术的结直肠癌（CRC）使用患者源性原发性肿瘤细胞分离与i-CR技术，优化CR方法。我们探索了使用i-CR平台指导CRC化疗的临床可行性，并建立了体外药物敏感性与患者临床反应的相关性。采用i-CR技术分离和培养原代CRC肿瘤细胞。进行NGS，并将i-CR细胞的WES和CNV结果与原始患者肿瘤样品的WES和CNV结果进行比较。体外药物筛选与指导化疗药物的CRC。用配对的PDX小鼠模型检查体内药物反应。进行了一项双盲联合临床队列研究，并将入组患者的临床结局与i-CR结果进行了比较。i-CR平台可用于快速繁殖原代结直肠肿瘤细胞，通过保持克隆异质性和遗传特征，有效地代表个体患者肿瘤。用i-CR细胞进行的化疗药物筛选与PDX模型相当。更重要的是，i-CR结果与入组CRC患者的临床结局高度一致。i-CR平台能够在临床前测试和优化治疗方案，研究癌细胞生物学，并建立肿瘤复发模型，以从有效的个性化医疗角度确定新的靶向治疗方法。
Established a new in vitro tumor model called novel conditionally reprogrammed (termed i-CR). Accomplished personalized drug tests within 2–3 weeks. Achieved 100% sensitivity, 85.7% specificity, 91.7% positive predictive value, and 100% negative predictive value. i-CR guided a inoperable patient with metastases converted to radical surgery. In vitro patient tumor models such as patient-derived organoids (PDO) and conditionally reprogrammed (CR) cell culture are important for translational research and pre-clinical drug testing. In this study we present a personalized drug sensitivity test for late stage, potentially operable colorectal cancer (CRC) using patient-derived primary tumor cells isolated with i-CR technology, an optimized CR method. We explored the clinical feasibility of using i-CR platform to guide CRC chemotherapy, and established the correlation between in vitro drug sensitivity and patient clinical response. Primary CRC tumor cells were isolated and cultured with the i-CR technology. NGS was performed and the WES and CNV results of i-CR cells were compared with that of the original patient tumor samples. In vitro drug screenings were done with guideline chemotherapy drugs for CRC. In vivo drug response was examined with paired PDX mouse models. A double-blind co-clinical cohort study was carried out and the clinical outcomes of the enrolled patients were compared with the i-CR results. i-CR platform could be used to rapidly propagate primary colorectal tumor cells that represent individual patient tumors effectively by keeping the clonal heterogeneity and the genetic characteristics. Chemotherapy drug screenings with i-CR cells were comparable with that of PDX models. More importantly, i-CR results showed high accordance with the clinical outcomes of the enrolled CRC patients. i-CR platform was capable to test and optimize therapeutic regimens pre-clinically, study cancer cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.
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影响因子：
82.9
作者：
Gao, Hui;Korn, Joshua M.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
3.7
作者：
Han SW;Kim HP;Shin JY;Jeong EG;Lee WC;Lee KH;Won JK;Kim TY;Oh DY;Im SA;Bang YJ;Jeong SY;Park KJ;Park JG;Kang GH;Seo JS;Kim JI;Kim TY
通讯作者：
Kim TY
影响因子：
4.3
作者：
Kim, Jung Han
通讯作者：
Kim, Jung Han
影响因子：
45.3
作者：
Goldberg, RM;Sargent, DJ;Alberts, SR
通讯作者：
Alberts, SR
患者来源的类器官模型有助于定义胃肠癌的个性化管理。
DOI：
10.1002/bjs.10726
发表时间：
2018-01
期刊：
The British journal of surgery
影响因子：
--
作者：
Aberle MR;Burkhart RA;Tiriac H;Olde Damink SWM;Dejong CHC;Tuveson DA;van Dam RM
通讯作者：
van Dam RM