Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

被引:0
作者
Zhang, Piyan [1 ]
Kovtun, Irina, V [1 ,2 ]
机构
[1] Mayo Clin, Ctr Individualized Med, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA
来源
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS | 2020年 / 161期
关键词
TUMOR XENOGRAFTS; ORTHOTOPIC XENOGRAFTS; DRUG RESPONSE; GROWTH; MODELS; MICE; HETEROGENEITY; METASTASIS; EXPRESSION; INHIBITOR;
D O I
10.3791/60646
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We present here an integrative approach for testing efficacy of targeted therapies that combines the next generation sequencing technolo-gies, therapeutic target analyses and drug response monitoring using patient derived xenografts (PDX). This strategy was validated using ovarian tumors as an example. The mate-pair next generation sequencing (MPseq) protocol was used to identify structural alterations and followed by analysis of potentially targetable alterations. Human tumors grown in immunocompromised mice were treated with drugs selected based on the genomic analyses. Results demonstrated a good correlation between the predicted and the observed responses in the PDX model. The presented approach can be used to test the efficacy of combination treatments and aid personalized treatment for patients with recurrent cancer, specifically in cases when standard therapy fails and there is a need to use drugs off label.
引用
收藏
页码:1 / 19
页数:19
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