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

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.