Salk Institute for Biological Studies, La Jolla, CA.
J Exp Med. 2022 Jun 6;219(6). doi: 10.1084/jem.20211505. Epub 2022 May 6.
Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers and is projected to soon be the second leading cause of cancer death. Median survival of PDA patients is 6-10 mo, with the majority of diagnoses occurring at later, metastatic stages that are refractory to treatment and accompanied by worsening prognoses. Glycosylation is one of the most common types of post-translational modifications. The complex landscape of glycosylation produces an extensive repertoire of glycan moieties, glycoproteins, and glycolipids, thus adding a dynamic and tunable level of intra- and intercellular signaling regulation. Aberrant glycosylation is a feature of cancer progression and influences a broad range of signaling pathways to promote disease onset and progression. However, despite being so common, the functional consequences of altered glycosylation and their potential as therapeutic targets remain poorly understood and vastly understudied in the context of PDA. In this review, the functionality of glycans as they contribute to hallmarks of PDA are highlighted as active regulators of disease onset, tumor progression, metastatic capability, therapeutic resistance, and remodeling of the tumor immune microenvironment. A deeper understanding of the functional consequences of altered glycosylation will facilitate future hypothesis-driven studies and identify novel therapeutic strategies in PDA.
胰腺导管腺癌（PDA）是最致命的癌症之一，预计很快将成为癌症死亡的第二大主要原因。PDA 患者的中位生存期为 6-10 个月，大多数诊断发生在晚期转移阶段，这些阶段对治疗具有抗药性，并伴有预后恶化。糖基化是最常见的翻译后修饰类型之一。糖基化的复杂景观产生了广泛的聚糖部分、糖蛋白和糖脂，从而增加了细胞内和细胞间信号调节的动态和可调水平。异常糖基化是癌症进展的一个特征，并影响广泛的信号通路，以促进疾病的发生和进展。然而，尽管这种情况很常见，但改变的糖基化的功能后果及其作为治疗靶点的潜力在 PDA 背景下仍然知之甚少，研究也远远不够。在这篇综述中，作为 PDA 特征的标志，糖的功能被强调为疾病发生、肿瘤进展、转移能力、治疗抵抗以及肿瘤免疫微环境重塑的积极调节剂。更深入地了解糖基化改变的功能后果将有助于未来基于假说的研究，并确定 PDA 中的新治疗策略。
