胰腺导管腺癌（PDAC）是一种治疗选择有限、长期存活率极低的癌症，预计将在2030年成为癌症相关死亡的第二大主因。这种癌症之所以如此侵袭性和抗药性，其中一个原因就是形成了包围新生上皮组织的密集基质，该基质促进了肿瘤的进展、侵袭、转移和抗药性。PDAC基质的三个主要组成部分是细胞外基质（ECM）、癌相关成纤维细胞（CAFs）和血管。密集的ECM充当自然物理屏障，阻碍药物渗透到PDAC肿瘤细胞中。因此，结合基质靶向和抗癌治疗的方法可能是增加药物渗透的可行选择。此外，血管是肿瘤基质的关键实体，是营养的通道，也是化学药物和免疫细胞发挥作用的唯一途径。最后，PDAC的CAFs和肿瘤细胞在肿瘤微环境中有着交流作用，它们负责增加基质沉积。在本综述中，我们旨在概述PDAC基质的三个关键组成部分和PDAC的新的有前途的治疗靶标。© 2022。作者（经University of Navarra专属许可）

Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with limited treatment options and terrible long-term survival, and it is expected to become the second leading cause of cancer-related death by 2030. One reason why this cancer is so aggressive and resistant is the formation of dense stroma that surrounds the neoplastic epithelium, which promotes tumor progression, invasion, metastasis, and resistance. The three major components of PDAC stroma are extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), and vasculature. The dense ECM acts as a natural physical barrier, impeding drug penetration to PDAC tumor cells. Consequently, the method that combines stroma-targeting with anticancer therapy may be a viable alternative for increasing drug penetration. Additionally, blood vessels are key entities of the tumor stroma, serving as a pathway for nutrition as well as the only way for chemical medicines and immune cells to act. Finally, PDAC CAFs and tumor cells have crosstalk effects in the tumor microenvironment, where they are responsible for enhanced matrix deposition. In this review, we aim to provide an overview of our current comprehension of the three key components of PDAC stroma and the new promising therapeutic targets for PDAC.© 2022. The Author(s) under exclusive licence to University of Navarra.