Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a very poor prognosis. Despite advancements in treatment strategies, PDAC remains recalcitrant to therapies because patients are often diagnosed at an advanced stage. The advanced stage of PDAC is characterized by metastasis, which typically renders it unresectable by surgery or untreatable by chemotherapy. The tumor microenvironment (TME) of PDAC comprises highly proliferative myofibroblast-like cells and hosts the intense deposition of a extracellular matrix component that forms dense fibrous connective tissue, a process called the desmoplastic reaction. In desmoplastic TMEs, the incessant aberration of signaling pathways contributes to immunosuppression by suppressing antitumor immunity. This feature offers a protective barrier that impedes the targeted delivery of drugs. In addition, the efficacy of immunotherapy is compromised because of the immune cold TME of PDAC. Targeted therapy approaches towards stromal and immunosuppressive TMEs are challenging. In this review, we discuss cellular and non-cellular TME components that contain actionable targets for drug development. We also highlight findings from preclinical studies and provide updates about the efficacies of new investigational drugs in clinical trials.
胰腺导管腺癌（PDAC）是一种高度致命的恶性肿瘤，预后极差。尽管治疗策略有所进展，但PDAC仍难以治愈，因为患者通常在晚期才被确诊。PDAC晚期以转移为特征，这通常导致其无法通过手术切除或化疗治疗。PDAC的肿瘤微环境（TME）包含高度增殖的肌成纤维细胞样细胞，并伴有大量细胞外基质成分沉积，形成致密的纤维结缔组织，这一过程称为促结缔组织增生反应。在促结缔组织增生的TME中，信号通路的持续异常通过抑制抗肿瘤免疫导致免疫抑制。这一特征形成了一道保护屏障，阻碍了药物的靶向递送。此外，由于PDAC的免疫冷TME，免疫疗法的疗效也受到影响。针对基质和免疫抑制TME的靶向治疗方法具有挑战性。在本综述中，我们讨论了包含药物开发可行靶点的细胞和非细胞TME成分。我们还重点介绍了临床前研究的结果，并提供了新研究药物在临床试验中疗效的最新信息。
肿瘤(癌症)患者之家