Department of Gastroenterology, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
Department of Pharmacy, National and Kapodistrian University of Athens, Athens GR 15772, Greece.
World J Gastroenterol. 2021 Jun 28;27(24):3568-3580. doi: 10.3748/wjg.v27.i24.3568.
Pancreatic cancer is one of the highest and in fact, unchanged mortality-associated tumor, with an exceptionally low survival rate due to its challenging diagnostic approach. So far, its treatment is based on a combination of approaches (such as surgical resection with or rarely without chemotherapeutic agents), but with finite limits. Thus, looking for additional space to improve pancreatic tumorigenesis therapeutic approach, research has focused on gene therapy with unexpectedly growing horizons not only for the treatment of inoperable pancreatic disease, but also for its early stages. gene delivery viral vectors, despite few disadvantages (possible immunogenicity, toxicity, mutagenicity, or high cost), could be one of the most efficient cancer gene therapeutic strategies for clinical application due to their superiority compared with other systems ( delivery strategies). Their dominance consists of simple preparation, easy operation and a wide range of functions. Adenoviruses are one of the most common used vectors, inducing strong immune as well as inflammatory reactions. Oncolytic virotherapy, using the above mentioned viral vectors, is one of the most promising non-pathogenic, highly-selective cytotoxic anti-cancer therapy using anti-cancer agents with high anti-tumor potency and strong oncolytic effect. There have been a variety of targeted therapeutic and pre-clinical strategies tested for gene therapy in pancreatic cancer such as gene-editing systems (, clustered regularly interspaced palindromic repeats-Cas9), RNA interference technology (, microRNAs, short hairpin RNA or small interfering RNA), adoptive immunotherapy and vaccination (, chimeric antigen receptor T-cell therapy) with encouraging results.
胰腺癌是死亡率最高的肿瘤之一,实际上死亡率并没有改变,其诊断方法极具挑战性,因此存活率极低。到目前为止,其治疗方法主要是结合多种方法(如手术切除加或不加化疗药物),但有一定的局限性。因此,为了寻找更多的方法来改善胰腺癌的治疗效果,研究人员将重点放在基因治疗上,这一领域的研究前景令人意外,不仅适用于无法手术的胰腺疾病,也适用于早期胰腺癌。 尽管病毒载体(如腺病毒)存在一些缺点(可能具有免疫原性、毒性、致突变性或高成本),但与其他系统( 递送策略)相比,它们具有优越性,因此可能成为最有效的癌症基因治疗策略之一,可用于临床应用。腺病毒是最常用的载体之一,可诱导强烈的免疫和炎症反应。溶瘤病毒治疗是利用上述 病毒载体,使用高抗肿瘤效力和强大溶瘤作用的抗癌药物进行非致病、高选择性细胞毒性抗癌治疗的最有前途的方法之一。已经有多种针对胰腺癌的基因治疗的靶向治疗和临床前策略进行了测试,如基因编辑系统(, 簇状规律间隔短回文重复序列-Cas9)、RNA 干扰技术(, 微小 RNA、短发夹 RNA 或小干扰 RNA)、过继免疫治疗和疫苗接种(, 嵌合抗原受体 T 细胞治疗),取得了令人鼓舞的结果。