Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis.
Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis.
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DOI：
10.3892/mmr.2017.7213
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Jin K
中科院分区：
文献类型：
--
作者：
Guan Z;Lan H;Chen X;Jiang X;Wang X;Jin K
传统的放化疗对胰腺癌的疗效仍然有限，目前还没有有效的靶向治疗或筛查试验。因此，胰腺癌的临床治疗需要更多的个体化药物筛选。建立胰腺癌骨转移的患者来源的异种移植物（PDX）模型，并使用下一代测序（NGS）来研究癌症的分子特征并筛选潜在的药物。进行免疫组织化学分析以验证PDX保留了患者的分子特征。使用NGS技术，从测序的416个基因中鉴定出13个胰腺癌相关的多态性/突变。根据测序结果和相关文献，选择AZD 6244作为潜在的治疗药物，AZD 6244是一种高选择性的丝裂原活化蛋白激酶激酶1（MEK 1）抑制剂。AZD 6244是一种高度选择性的MEK 1抑制剂，被评估为对胰腺癌PDX模型有效，因此可能在本研究中研究的胰腺癌患者的临床治疗中提供潜在疗效。新的基于NGS-PDX的药物筛选模式的可行性得到了证明，并有可能改善癌症的个体化治疗。
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.