Pancreatic ductal adenocarcinoma (PDAC) belongs to the most lethal solid tumors in humans. A histological hallmark feature of PDAC is the pronounced tumor microenvironment (TME) that dynamically evolves during tumor progression. The TME consists of different non-neoplastic cells such as cancer-associated fibroblasts (CAFs), immune cells, endothelial cells and neurons. Furthermore, abundant extracellular matrix (ECM) components such as collagen and hyaluronic acid (HA) as well as matricellular proteins create a highly dynamic and hypovascular TME with multiple biochemical and physical interactions among the various cellular and acellular components that promote tumor progression and therapeutic resistance. In recent years, intensive research efforts have resulted in a significantly improved understanding of the biology and pathophysiology of the TME in PDAC, and novel stroma-targeted approaches are emerging that may help to improve the devastating prognosis of PDAC patients. However, none of anti-stromal therapies have been approved in patients so far, and there is still a large discrepancy between multiple successful preclinical results and subsequent failure in clinical trials. Furthermore, recent findings suggest that parts of the TME may also possess tumor-restraining properties rendering tailored therapies even more challenging.

中文翻译：

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胰腺癌的微环境决定因素。

胰腺导管腺癌（PDAC）属于人类最致命的实体瘤。PDAC的组织学特征是明显的肿瘤微环境（TME），它在肿瘤进展过程中动态演变。TME由不同的非肿瘤细胞组成，例如癌症相关的成纤维细胞（CAF），免疫细胞，内皮细胞和神经元。此外，丰富的细胞外基质（ECM）成分（例如胶原蛋白和透明质酸（HA））以及基质细胞蛋白可形成高度动态的血管下TME，在各种细胞和无细胞成分之间具有多种生化和物理相互作用，从而促进肿瘤的发展和治疗抵抗力。最近几年，大量的研究工作已大大改善了对PDAC中TME的生物学和病理生理学的了解，并且涌现了针对多种基质的新方法，这些方法可能有助于改善PDAC患者的毁灭性预后。但是，到目前为止，尚无一种抗基质疗法被批准用于患者，并且多次成功的临床前结果与随后的临床试验失败之间仍然存在巨大差异。此外，最近的发现表明，TME的某些部分还可能具有抑制肿瘤的特性，使量身定制的疗法更具挑战性。而且在临床试验中多次成功的临床前结果与随后的失败之间仍然存在巨大差异。此外，最近的发现表明，TME的某些部分还可能具有抑制肿瘤的特性，使量身定制的疗法更具挑战性。而且在临床试验中多次成功的临床前结果与随后的失败之间仍然存在巨大差异。此外，最近的发现表明，TME的某些部分可能还具有抑制肿瘤的特性，从而使定制疗法更具挑战性。