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Characterization of drug responses of mini patient-derived xenografts in mice for predicting cancer patient clinical therapeutic response

Authors
  • Zhang, Feifei1
  • Wang, Wenjie1
  • Long, Yuan1
  • Liu, Hui1
  • Cheng, Jijun1
  • Guo, Lin1
  • Li, Rongyu1
  • Meng, Chao1
  • Yu, Shan1
  • Zhao, Qingchuan2
  • Lu, Shun3
  • Wang, Lili4
  • Wang, Haitao4
  • Wen, Danyi1
  • 1 Shanghai LIDE Biotech Co., LTD, Shanghai, 201203, P. R. China , Shanghai (China)
  • 2 The Fourth Military Medical University, Department of Surgery, Xijing Hospital, Xi’an, 710032, P. R. China , Xi’an (China)
  • 3 Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Department of Oncology, Shanghai, 200030, P. R. China , Shanghai (China)
  • 4 The Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Urology, Tianjin, 300211, P. R. China , Tianjin (China)
Type
Published Article
Journal
Cancer Communications
Publisher
BioMed Central
Publication Date
Sep 26, 2018
Volume
38
Issue
1
Identifiers
DOI: 10.1186/s40880-018-0329-5
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundPatient-derived organoids and xenografts (PDXs) have emerged as powerful models in functional diagnostics with high predictive power for anticancer drug response. However, limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy, and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic. The present study aimed to develop an advanced PDX model, namely MiniPDX, for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment.MethodsWe developed a rapid in vivo drug sensitivity assay, OncoVee® MiniPDX, for screening clinically relevant regimens for cancer. In this model, patient-derived tumor cells were arrayed within hollow fiber capsules, implanted subcutaneously into mice and cultured for 7 days. The cellular activity morphology and pharmacokinetics were systematically evaluated. MiniPDX performance (sensitivity, specificity, positive and negative predictive values) was examined using PDX as the reference. Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively. The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes.ResultsMorphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors. Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients, including 14 gastric cancer, 10 lung cancer and 2 pancreatic cancer. The positive predictive value of MiniPDX was 92%, and the negative predictive value was 81% with a sensitivity of 80% and a specificity of 93%. Through expanding to clinical tumor samples, MiniPDX assay showed potential of wide clinical application.ConclusionsFast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens. The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay, as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment.

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