Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis

Guan,Zhonghai; Lan,Huanrong; Chen,Xiangheng; Jiang,Xiaoxia; Wang,Xuanwei; Jin,Ketao

doi:10.3892/mmr.2017.7213

October-2017 Volume 16 Issue 4

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October-2017 Volume 16 Issue 4

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Article Open Access

Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis

Authors:
- Zhonghai Guan
- Huanrong Lan
- Xiangheng Chen
- Xiaoxia Jiang
- Xuanwei Wang
- Ketao Jin
View Affiliations / Copyright

Affiliations: Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China, Department of Breast and Thyroid Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China, Department of Minimally Invasive Surgery, The 2nd Xiangya Hospital of Central South University, Chansha, Hunan 421001, P.R. China, Department of Surgical Oncology, The 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Orthopedics, The 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China

Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 4784-4790
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Published online on: August 10, 2017

https://doi.org/10.3892/mmr.2017.7213
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Abstract

The efficacy of traditional chemoradiotherapies for pancreatic cancer remains limited, and no effective targeted therapies or screening tests are currently available. Therefore more individualized drug screening is warranted for the clinical treatment of pancreatic cancer. A patient‑derived xenograft (PDX) model of pancreatic cancer bone metastasis was established, and next‑generation sequencing (NGS) was used to investigate the molecular characteristics of the cancer and screen for potential drugs. Immunohistochemical analysis was performed to validate that the PDX retained the molecular characteristics from the patient. Using NGS technology, 13 pancreatic‑cancer‑associated polymorphisms/mutations were identified out of 416 genes sequenced. Based on the sequencing results and associated literatures, AZD6244, a highly selective inhibitor against mitogen‑activated protein kinase kinase 1 (MEK1), was chosen as a potential therapy. AZD6244, a highly selective MEK1 inhibitor, was evaluated as effective for the pancreatic cancer PDX model, and thus may provide potential efficacy in the clinical treatment of the patient with pancreatic cancer investigated in the present study. The feasibility of the novel NGS‑PDX based drug‑screening pattern was demonstrated, and has a potential to improve individualized treatment for cancer.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis

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Abstract

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