Weng Ching-Chieh, Lin Yu-Chun, Cheng Kuang-Hung
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
J Clin Med. 2019 Sep 2;8(9):1369. doi: 10.3390/jcm8091369.
Pancreatic cancer is often treatment-resistant, with the emerging standard of care, gemcitabine, affording only a few months of incrementally-deteriorating survival. Reflecting on the history of failed clinical trials, genetically engineered mouse models (GEMMs) in oncology research provides the inspiration to discover new treatments for pancreatic cancer that come from better knowledge of pathogenesis mechanisms, not only of the derangements in and consequently acquired capabilities of the cancer cells, but also in the aberrant microenvironment that becomes established to support, sustain, and enhance neoplastic progression. On the other hand, the existing mutational profile of pancreatic cancer guides our understanding of the disease, but leaves many important questions of pancreatic cancer biology unanswered. Over the past decade, a series of transgenic and gene knockout mouse modes have been produced that develop pancreatic cancers with features reflective of metastatic pancreatic ductal adenocarcinoma (PDAC) in humans. Animal models of PDAC are likely to be essential to understanding the genetics and biology of the disease and may provide the foundation for advances in early diagnosis and treatment.
胰腺癌通常具有抗药性，目前的标准治疗药物吉西他滨仅能使患者存活期延长几个月，且生存质量逐渐下降。回顾过去临床试验失败的历史，肿瘤学研究中的基因工程小鼠模型（GEMMs）为发现胰腺癌的新治疗方法提供了灵感，这源于对发病机制的更深入了解，不仅包括癌细胞的紊乱及其由此获得的能力，还包括为支持、维持和促进肿瘤进展而形成的异常微环境。另一方面，胰腺癌现有的突变谱有助于我们理解这种疾病，但仍有许多关于胰腺癌生物学的重要问题尚未得到解答。在过去十年中，已经产生了一系列转基因和基因敲除小鼠模型，这些模型所患的胰腺癌具有人类转移性胰腺导管腺癌（PDAC）的特征。PDAC动物模型对于理解该疾病的遗传学和生物学可能至关重要，并可能为早期诊断和治疗的进展提供基础。
