Cancer Communications
indexed by SCI
BMC

Original article
Personalized treatment based on mini patient-derived xenografts and WES/RNA sequencing in a patient with metastatic duodenal adenocarcinoma
Peng Zhao, Hui Chen, Danyi Wen, Shuo Mou, Feifei Zhang and Shusen Zheng
1.Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003, P. R. China
[Abstract]

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 treatments) 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 cisplatin, 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.
Cancer Communications   Epub date: 9/12/2018   doi:10.1186/s40880-018-0323-y   [ PDF Full-text ]   

CJC Wechat 微信公众号


 

Editorial Manager


CC adopts Editorial Manager to manage its submissions from Dec.18, 2014

 Submission Guidelines  

 

Reference style for  

 EndNote,
 Reference Manager



Editorial Manager


 

Year:

 

Month:

Advanced search

Subscription


CC is now published by BioMed Central

© Cancer Communications

651 Dongfeng Road East, Guangzhou 510060, P. R. China