Understanding Disease Biology and Informing the Management of Pancreas Cancer With Preclinical Model Systems.
Understanding Disease Biology and Informing the Management of Pancreas Cancer With Preclinical Model Systems.
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DOI：
10.1097/ppo.0000000000000289
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Hingorani SR
中科院分区：
文献类型：
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作者：
Whittle MC;Hingorani SR
胰腺导管腺癌(PDA)细胞毒治疗的最新进展被更有针对性的治疗策略的临床进展所掩盖，其中绝大多数在临床试验中都失败了。无法将临床前承诺转化为临床疗效的部分原因是疾病建模不完善以及临床前和临床研究设计和执行之间的不匹配。进入这些缺口的是我们的患者，他们满怀期待地进入临床试验场景，并首当其冲地承受其不足之处。如果改善患者存活率是最重要的，那么必须承认，3期试验的失败代表着之前所有工作的更大失败。反复的失败表明有必要重新评估目前的临床前到临床设备。研究人员现在可以使用特殊型号的PDA，迈向成功新时代的第一步可以从改进这些系统的选择和应用开始。在这里，我们讨论了PDA的主要临床前平台的主要特征，并提出了一个严格询问预期治疗的范例。
Recent advances in cytotoxic therapies for pancreatic ductal adenocarcinoma (PDA) are overshadowed by stalled clinical progress of more targeted strategies, the vast majority of which have failed in clinical trials. Inability to translate preclinical promise into clinical efficacy derives, in part, from imperfect disease modeling and mismatches between preclinical and clinical study design and execution. Into these gaps fall our patients who enter the clinical trial landscape expectantly and bear the brunt of its inadequacies. If improving patient survival is paramount, then it must be acknowledged that the failure of a Phase 3 trial represents a larger failure of all of the work that preceded it. Repeated failures suggest a need to reappraise the current preclinical-to-clinical apparatus. Exceptional models of PDA are now available to researchers and the first steps toward a new era of success can begin with improved selection and application of these systems. Herein we discuss the key features of the major preclinical platforms for PDA and propose a paradigm for rigorous interrogation of prospective therapies.