A potential novel therapy for FGFR1‑amplified pancreatic cancer with bone metastasis, screened by next‑generation sequencing and a patient‑derived xenograft model

Guan,Zhonghai; Lan,Huanrong; Sun,Dan; Wang,Xuanwei; Jin,Ketao

doi:10.3892/ol.2018.9876

A potential novel therapy for FGFR1‑amplified pancreatic cancer with bone metastasis, screened by next‑generation sequencing and a patient‑derived xenograft model

Authors:
- Zhonghai Guan
- Huanrong Lan
- Dan Sun
- Xuanwei Wang
- Ketao Jin
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Affiliations: Department of Colorectal Surgery, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, P.R. China, Department of Breast and Thyroid Surgery, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, P.R. China, Zhejiang Center of Medical Academic Exchange, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China, Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China
Published online on: December 28, 2018 https://doi.org/10.3892/ol.2018.9876
Pages: 2303-2307
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Effective therapies are limited for pancreatic cancer, particularly for those with distant tumour metastases. Therefore, more individualised drug screening is urgently required. Next‑generation sequencing (NGS) is a powerful tool to investigate the genomic landscape of patients and the mechanism of drug response, which may provide a broader vision for potential clinical drug screening. Patient‑derived xenograft (PDX) models may have a significant advantage in predicting clinical treatment response. In our previous study, a PDX of pancreatic cancer bone metastasis was established, and NGS was conducted to investigate the molecular information. In the present study, these data were further analysed and fibroblast growth factor receptor 1 (FGFR1) amplification was identified in a panel of 416 cancer‑associated genes. Thus, AZD4547, an inhibitor against FGFR, was selected as a potential therapy, and was evaluated using the PDX model. AZD4547 was shown to exhibit antitumor activity by reducing the expression of FGFR1 and its targets. The present study also demonstrated the high potential of the novel NGS/PDX‑based drug screening platform to improve individualised cancer treatment.

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