利用结直肠癌肝转移患者来源的异种移植模型预测化疗敏感性。

Using patient-derived xenograft models of colorectal liver metastases to predict chemosensitivity.

作者信息

Brown Kai M, Xue Aiqun, Julovi Sohel M, Gill Anthony J, Pavlakis Nick, Samra Jaswinder S, Smith Ross C, Hugh Thomas J

机构信息

Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Northern Clinical School, University of Sydney, Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, New South Wales, Australia.

出版信息

J Surg Res. 2018 Jul;227:158-167. doi: 10.1016/j.jss.2018.02.018. Epub 2018 Mar 15.

DOI:10.1016/j.jss.2018.02.018

PMID:29804848

Abstract

BACKGROUND

Few in vivo models for colorectal cancer have been demonstrated to show external validity by accurately predicting clinical patient outcomes. Patient-derived xenograft (PDX) models of cancer have characteristics that might provide a form of translational research leading to personalized cancer care. The aim of this pilot study was to assess the feasibility of using PDXs as a platform for predicting patient colorectal liver metastases responses, in this case by correlating PDX and patient tumor responses to either folinic acid, fluorouracil plus oxaliplatin or folinic acid, fluorouracil plus irinotecan-based regimens.

METHODS

Sixteen patients underwent potentially curative resection of colorectal liver metastases, and tumors were grafted into NOD.CB17-Prkdc/Arc mice. Mice were divided into groups to determine relative tumor growth in response to treatment. Tumors were analyzed by immunohistochemistry for Ki67 and Excision repair cross-complementation group 1.

RESULTS

An engraftment rate of 81% was achieved. Overall, there was a 67% positive match rate between eligible patient and PDX chemosensitivity profiles. There was a significant difference in relative decrease in Ki67 expression between sensitive/stable versus resistant PDXs for both treatment regimens. There was no statistically significant correlation between baseline ERCC1 expression and response to Oxaliplatin + 5-Fluorouracil in the PDXs.

CONCLUSIONS

This pilot study supports the feasibility of using PDX models of advanced colorectal cancer in larger studies to potentially predict patient chemosensitivity profiles.

摘要

背景

很少有结直肠癌的体内模型被证明能通过准确预测临床患者的预后显示出外部有效性。患者来源的异种移植（PDX）癌症模型具有一些特征，可能为导致个性化癌症治疗的转化研究提供一种形式。这项初步研究的目的是评估使用PDX作为预测患者结直肠癌肝转移反应的平台的可行性，在本研究中，通过将PDX和患者肿瘤对亚叶酸、氟尿嘧啶加奥沙利铂或亚叶酸、氟尿嘧啶加伊立替康方案的反应进行关联。