Rahman Md Ataur, Ahmed Kazi Rejvee, Rahman M D Hasanur, Parvez Md Anowar Khasru, Lee In-Seon, Kim Bonglee
Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 02447, Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Biomedicines. 2022 Jun 20;10(6):1459. doi: 10.3390/biomedicines10061459.
Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy's dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.
胰腺癌（PC）起源于胰腺器官，胰腺可产生消化酶，它是亟需合适治疗策略的严重癌症之一。自噬发生在PC组织的多个区域，包括癌细胞、癌症相关成纤维细胞和免疫细胞，并且可由各种促进和抑制信号进行微调。因此，自噬对胰腺癌发生和进展的影响在很大程度上取决于其阶段和条件。在初始阶段，自噬抑制肿瘤前损伤的进展。然而，在发展阶段，自噬促进肿瘤形成。几项研究报告称，自噬在癌症中的促肿瘤和抑肿瘤功能可能都取决于细胞类型。然而，自噬对于胰腺导管腺癌（PDAC）的生长并非必需，并且使用自噬抑制剂的临床试验，无论是单独使用还是与其他疗法联合使用，取得的成功都有限。尽管自噬抑制剂在医学研究中延长了寿命，但自噬的双重作用模式使其在治疗上具有挑战性，这凸显了对当前研究结果进行更严格审查以及采用更精确靶向策略的必要性。确实，自噬在PC中的作用很复杂，从实验室到临床应用时必须考虑众多因素。在本综述中，我们总结了自噬在PC肿瘤发生中的致瘤和保护作用的证据，并描述了在理解PDAC中自噬如何被调节和控制方面的最新进展。
