Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
Biomed Pharmacother. 2020 Dec;132:110799. doi: 10.1016/j.biopha.2020.110799. Epub 2020 Oct 6.
Pancreatic cancer is a malignancy with extremely low five-year survival rate. Pancreatic tumors maintain a high basal level of autophagy for survival and progression. Autophagy dysfunction leads to tumor progression in pancreatic cancer patients. Clinical trials with autophagy inhibitors, including hydroxychloroquine and chloroquine, showed no significant therapeutic benefit as monotherapy. Instead of using chemical inhibitors, microRNA may serve as an alternative approach for autophagy inhibition. In the context of pancreatic cancer, the feasibility of using the microRNA approach to target core autophagy-related genes has been shown, which results in suppression of initiation or flux blockage of autophagy. In addition, autophagy inhibition leads to increased sensitivity of pancreatic tumors to a variety of therapeutic approaches, including radiotherapy, chemotherapy and other targeted agents. Recent studies suggest microRNA-based autophagy inhibition can be a promising and feasible approach for the clinical care of pancreatic cancer patients. Here we reviewed the mechanism of autophagy and recent progress of autophagy inhibition in pancreatic cancer treatment. We particularly focus on the microRNA approach in autophagy inhibition in pancreatic cancer.
胰腺癌是一种恶性肿瘤，五年生存率极低。胰腺肿瘤为了生存和进展维持着高水平的基础自噬。自噬功能障碍导致胰腺癌患者的肿瘤进展。使用自噬抑制剂（包括羟氯喹和氯喹）的临床试验作为单一疗法并没有显示出显著的治疗益处。与其使用化学抑制剂，miRNA 可能是一种替代的自噬抑制方法。在胰腺癌的背景下，已经证明了使用 miRNA 方法靶向核心自噬相关基因的可行性，这导致自噬的起始或通量阻断受到抑制。此外，自噬抑制导致胰腺肿瘤对各种治疗方法（包括放疗、化疗和其他靶向药物）的敏感性增加。最近的研究表明，基于 miRNA 的自噬抑制可能是一种有前途和可行的方法，用于胰腺癌患者的临床护理。在这里，我们综述了自噬的机制以及自噬抑制在胰腺癌治疗中的最新进展。我们特别关注 miRNA 方法在胰腺癌自噬抑制中的作用。
