Medicum, Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland.
Research Programs Unit, Translational Cancer Medicine Program, University of Helsinki, Helsinki, Finland.
Adv Exp Med Biol. 2020;1233:101-115. doi: 10.1007/978-3-030-38266-7_4.
The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), has a dismal 5-year survival rate of less than 5%. Radical surgical resection, in combination with adjuvant chemotherapy, provides the best option for long-term patient survival. However, only approximately 20% of patients are resectable at the time of diagnosis, due to locally advanced or metastatic disease. There is an urgent need for the identification of new, specific, and more sensitive biomarkers for diagnosis, prognosis, and prediction to improve the treatment options for pancreatic cancer patients. Dysregulation of proteostasis is linked to many pathophysiological conditions, including various types of cancer. In this review, we report on findings relating to the main cellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, in pancreatic cancer. The expression of several components of the proteolytic network, including E3 ubiquitin-ligases and deubiquitinating enzymes, are dysregulated in PDAC, which accounts for approximately 90% of all pancreatic malignancies. In the future, a deeper understanding of the emerging role of proteostasis in pancreatic cancer has the potential to provide clinically relevant biomarkers and new strategies for combinatorial therapeutic options to better help treat the patients.
最常见的胰腺癌形式是胰腺导管腺癌（PDAC），其 5 年生存率不到 5%。根治性手术切除结合辅助化疗是长期患者生存的最佳选择。然而，由于局部晚期或转移性疾病，只有约 20%的患者在诊断时可进行手术切除。迫切需要鉴定新的、特异性的和更敏感的生物标志物用于诊断、预后和预测，以改善胰腺癌患者的治疗选择。蛋白质稳态失调与许多病理生理状况有关，包括各种类型的癌症。在这篇综述中，我们报告了与主要细胞蛋白降解系统（泛素-蛋白酶体系统（UPS）和自噬）在胰腺癌中的关系的发现。蛋白酶解网络的几个组成部分的表达在 PDAC 中失调，占所有胰腺恶性肿瘤的约 90%。未来，更深入地了解蛋白质稳态在胰腺癌中的新兴作用有可能提供临床相关的生物标志物和新的联合治疗策略，以更好地帮助治疗患者。
