Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Br J Cancer. 2013 Jan 15;108(1):1-8. doi: 10.1038/bjc.2012.569. Epub 2013 Jan 8.
Pancreatic ductal adenocarcinomas (PDAs) are notoriously aggressive and resistant to treatment. They distinguish themselves further by their robust fibroinflammatory, or desmoplastic, stromal reaction and degree of hypovascularity. Recent findings have revealed multiple mechanisms of stromal complicity in disease pathogenesis and resistance. In this review, we focus on altered physicomechanics as one mechanism of what we term as 'stromal resistance' in PDA. Extremely high interstitial fluid pressures and a dense extracellular matrix combine to limit the delivery and distribution of therapeutic agents. We discuss the genesis and consequences of altered fluid dynamics in PDA and strategies to restore them.
胰腺导管腺癌（PDAs）是众所周知的侵袭性和耐药性肿瘤。它们还以其强大的纤维炎性或纤维母细胞性、基质反应和低血管生成程度为特征。最近的研究结果揭示了基质在疾病发病机制和耐药性中的多种复杂机制。在这篇综述中，我们重点关注物理化学性质的改变，这是我们所谓的 PDAs 中“基质耐药性”的一种机制。极高的细胞间液压力和致密的细胞外基质结合在一起，限制了治疗药物的输送和分布。我们讨论了 PDAs 中流体动力学改变的起源和后果，以及恢复它们的策略。
