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Personalized treatment based on mini patient-derived xenografts and WES/RNA sequencing in a patient with metastatic duodenal adenocarcinoma

查看全文 作　　者：Peng [1]Zhao;Hui [2]Chen;Danyi [3]Wen;Shuo [4]Mou;Feifei [3]Zhang;Shusen [5,6]Zheng 高影响力作者 机构地区：[1]Cancer Biotherapy Center,The First Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310003,P.R.China;[2]Department of General Surgery,Zhejiang Hospital,Hangzhou 310013,P.R.China;[3]LIDE Biotech Co.,Ltd,Shanghai,P.R.China;[4]OrigiMed Co.,Ltd,Shanghai,P.R.China;[5]Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,The First Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310003,P.R.China;[6]Key Lab of Combined Multi-Organ Transplantation,Ministry of Public Health,Hangzhou,China高影响力机构 出　　处：《Cancer Communications》索引2018年第38卷第1期,共7页高影响力期刊 基　　金：the National Natural Science Foundation of China(No.81472346);the National Key Research and Development Program of China(No.2017ZX10203205). 摘　　要：Background:Treatment guidelines for a variety of cancers have been increasingly used in clinical practice,and have resulted in major improvement in patient outcomes.However,recommended regimens(even first-line treat-ments)are clearly not ideal for every patients.In the present study,we used mini patient-derived xenograft(mini-PDX)and next-generation sequencing to develop personalized treatment in a patient with metastatic duodenal adenocarcinoma.Methods:Resected metachronous metastatic tumor tissues were implanted into SCID mice to determine the sensitivity to a variety of drug regimens.Mutation profiles were assessed using both DNA whole-exome sequencing(DNA-WES)and RNA sequencing.The results of the analyses were used to select optimal treatment for the patient with metastatic duodenal adenocarcinoma.Results:Assessment with mini-PDX models took only 7 days.The results showed high sensitivity to S-1 plus cis-platin,gemcitabine plus cisplatin and everolimus alone.The patient received gemcitabine plus cisplatin initially,but the treatment was terminated due to toxicity.The patient was then switched to treatment with S-1 alone.The overall disease-free survival was 34 months.DNA-WES and RNA sequencing identified KRAS mutation(A146T),TP53(C229Yfs*10)and RICTOR amplification in the metastatic duodenal adenocarcinoma.These findings provided further support to the results of the mini-PDX,and suggest mTOR inhibitors should be used if and when relapse eventually occurs in this patient.Conclusions:Mini-PDX model combined with WES/RNA sequencing can rapidly assess drug sensitivity in cancer patients and reveal key genetic alterations.Further research on this technology for personalized therapy in patients with refractory malignant tumors is warranted. 关 键 词：Duodenal adenocarcinoma Mini patient-derived xenograft Whole-exome sequencing RNA sequencing Somatic mutation Personalized therapy
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