Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors with an overall five-year survival rate of that has only just reached 10%. The tumor microenvironment of PDAC is characterized by desmoplasia, which consist of dense stroma of fibroblasts and inflammatory cells, resulting in a hypoxic environment due to limited oxygen diffusion through the tumor. Hypoxia contributes to the aggressive tumor biology by promoting tumor progression, malignancy, and promoting resistance to conventional and targeted therapeutic agents. In depth research in the area has identified that hypoxia modulates the tumor biology through hypoxia inducible factors (HIFs), which not only are the key determinant of pancreatic malignancy but also an important target for therapy. In this review, we summarize the recent advances in understanding hypoxia driven phenotypes, which are responsible for the highly aggressive and metastatic characteristics of pancreatic cancer, and how hypoxia can be exploited as a target for drug delivery.

胰腺导管腺癌（PDAC）仍然是最致命的实体瘤之一，其五年总生存率仅达到10％。PDAC的肿瘤微环境的特征是异型增生，其由成纤维细胞和炎性细胞的致密基质组成，由于氧在肿瘤中的扩散有限，导致缺氧环境。缺氧通过促进肿瘤进展，恶性肿瘤和增强对常规和靶向治疗剂的耐药性而促进了侵袭性肿瘤生物学。该领域的深入研究已经发现，低氧通过低氧诱导因子（HIF）调节肿瘤生物学，这不仅是胰腺恶性肿瘤的关键决定因素，而且还是治疗的重要靶点。在这篇评论中