靶向短肽药物在胰腺癌治疗中的应用及其作用机制  

Application and Mechanism of Drugs Targeting Short Peptide in The Treatment Pancreatic Cancer

作　　者：刘媛[1,2,3,4] 董雪迎 周策凡 唐景峰[1,2,3,4] LIU Yuan;DONG Xue-Ying;ZHOU Ce-Fan;TANG Jing-Feng(“111”Introduction Base of Cell Regulation and Molecular Medicine,Ministry of Science and Technology/Ministry of Education,Hubei University of Technology,Wuhan 430068,China;Key Laboratory of Fermentation Engineering,Ministry of Education,Hubei University of Technology,Wuhan 430068,China;Collaborative Innovation Center for Industrial Fermentation,Hubei University of Technology,Wuhan 430068,China;Hubei Provincial Key Laboratory of Industrial Microbiology,Hubei University of Technology,Wuhan 430068,China)

机构地区：[1]湖北工业大学科技部/教育部细胞调控与分子药物学科“111”引智基地,武汉430068 [2]湖北工业大学发酵工程教育部重点实验室,武汉430068 [3]湖北工业大学工业发酵省部共建协同创新中心,武汉430068 [4]湖北工业大学工业微生物湖北省重点实验室,武汉430068

出　　处：《生物化学与生物物理进展》2024年第9期2101-2114,共14页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(32000523,32070726)资助项目。

摘　　要：胰腺癌是一种致命的恶性肿瘤,其发病率和死亡率在不断上升,导致这种结果的原因主要是诊断晚、转移快、易耐药、缺乏有效的治疗方法。目前的治疗方法主要是手术切除、联合用药和化疗,但效果较差。因此,开发新的治癌药物迫在眉睫,精准治疗和靶向药物或将成为改善胰腺癌患者生存的新方向。靶向肽缓解了这些问题,显著提高了治疗效率和递送靶向性,作为新兴的靶向药物,其对胰腺癌具有较好的抑制效果,凭借自身的分子质量小、选择性高等特点受到了研究人员的广泛关注。短肽通过蛋白质间相互作用或直接穿膜到达目标靶点等多种机制诱导癌细胞死亡。临床上直接用药或联合化疗药物用于肿瘤治疗。本文针对靶向胰腺癌的短肽药物展开综述,总结了短肽在NF-κB、Wnt、自噬等信号通路中的作用机制——通过竞争性结合、抑制关键因子表达或改变通路活性达到抑癌效果,为胰腺癌治疗提供新的思路。Pancreatic cancer(PC)is a highly fatal disease which originated from pancreatic epithelial and acinar cells,and the survival rate of pancreatic cancer patients is only about 12%.Approximately 95%of pancreatic cancer presents as ductal adenocarcinoma(PDAC).Pancreatic cancer is characterized by high aggressiveness,rapid progression and progression,and high resistance to treatment.Common somatic mutated genes in the early stage of pancreatic cancer include KRAS,CDKN2A,TP53,and SMAD4.Most pancreatic cancer patients are affected by environmental risk factors such as age,sex and diet.Malignant pancreatic cancer is associated with non-invasive,preneoplastic lesions that are thoughted to be precursors,such as pancreatic intraepithelial neoplasia(PanIN),intraductal papillary mucinous neoplasm(IPMN)and mucinous cystadenoma(MCN).In recent years,people have gradually improved the therapy and diagnosis of pancreatic cancer,and the contribution of imaging technology,which enhancing the usage of minimally invasive pancreatectomy that typically includes pancreaticoduodenectomy and distal pancreatectomy.However,combined administration of the chemotherapeutic gemcitabine and erlotinib is still considered a potential first-line treatment for advanced pancreatic cancer,but the development of chemoresistance often leads to poor therapeutic outcomes.Based on the current research progress for pancreatic cancer,its treatment currently remains one of the most important challenges in the medical field.Although some new treatment options have been provided,there were minor clinical success achieved and therefore new safe and effective therapies of pancreatic cancer are still an urgent need for patients.Among these new therapies for pancreatic cancer,short peptide-based treatment protocols have attracted great attention.Peptide is a compound formed by linkingα-amino acids together in peptide chains.It is also an intermediate product of proteolysis.The short peptide-based therapy has many advantages such as precise targeting,easy preparatio

关 键 词：胰腺癌 短肽 靶向治疗 自噬 

分 类 号：Q291[生物学—细胞生物学] R73[医药卫生—肿瘤]