Fokas Emmanouil, O'Neill Eric, Gordon-Weeks Alex, Mukherjee Somnath, McKenna W Gillies, Muschel Ruth J
Department of Oncology, Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK.
Department of Oncology, Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK.
Biochim Biophys Acta. 2015 Jan;1855(1):61-82. doi: 10.1016/j.bbcan.2014.12.001. Epub 2014 Dec 7.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Despite improvements in the clinical management, the prognosis of PDAC remains dismal. In the present comprehensive review, we will examine the knowledge of PDAC genetics and the new insights into human genome sequencing and clonal evolution. Additionally, the biology and the role of the stroma in tumour progression and response to treatment will be presented. Furthermore, we will describe the evidence on tumour chemoresistance and radioresistance and will provide an overview on the recent advances in PDAC metabolism and circulating tumour cells. Next, we will explore the characteristics and merits of the different mouse models of PDAC. The inflammatory milieu and the immunosuppressive microenvironment mediate tumour initiation and treatment failure. Hence, we will also review the inflammatory and immune escaping mechanisms and the new immunotherapies tested in PDAC. A better understanding of the different mechanisms of tumour formation and progression will help us to identify the best targets for testing in future clinical studies of PDAC.
胰腺导管腺癌（PDAC）是癌症死亡的第四大主要原因。尽管临床管理有所改善，但PDAC的预后仍然很差。在本综述中，我们将研究PDAC遗传学知识以及人类基因组测序和克隆进化的新见解。此外，还将介绍基质在肿瘤进展和治疗反应中的生物学特性和作用。此外，我们将描述肿瘤化疗耐药性和放射抗性的证据，并概述PDAC代谢和循环肿瘤细胞的最新进展。接下来，我们将探讨不同PDAC小鼠模型的特点和优点。炎症环境和免疫抑制微环境介导肿瘤发生和治疗失败。因此，我们还将综述炎症和免疫逃逸机制以及在PDAC中测试的新免疫疗法。更好地理解肿瘤形成和进展的不同机制将有助于我们确定在未来PDAC临床研究中进行测试的最佳靶点。
