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.
Mol Med Rep. 2017 Oct;16(4):4784-4790. doi: 10.3892/mmr.2017.7213. Epub 2017 Aug 10.
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 individua-lized treatment for cancer.
传统的放化疗治疗胰腺癌的疗效仍然有限,目前也没有有效的靶向治疗或筛查试验。因此,更需要对胰腺癌的临床治疗进行个体化药物筛选。建立了胰腺癌骨转移患者来源的异种移植(PDX)模型,并采用下一代测序(NGS)技术来研究癌症的分子特征并筛选潜在药物。免疫组织化学分析验证了 PDX 保留了患者的分子特征。通过 NGS 技术,在测序的 416 个基因中鉴定出了 13 个与胰腺癌相关的多态性/突变。基于测序结果和相关文献,选择高度选择性的丝裂原活化蛋白激酶激酶 1(MEK1)抑制剂 AZD6244 作为潜在治疗药物。AZD6244 是一种高度选择性的 MEK1 抑制剂,对胰腺癌 PDX 模型有效,因此可能为研究中患者的胰腺癌临床治疗提供潜在疗效。新型 NGS-PDX 基础药物筛选模式的可行性已得到证实,有可能改善癌症的个体化治疗。