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Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

机译:胰腺癌基因治疗:从分子靶点到递送系统

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摘要

The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.
机译:对胰腺肿瘤细胞中关键通路失控的分子变化的持续鉴定为我们提供了许多新颖的候选基因,以设计基因靶向的胰腺癌治疗方法。基因治疗中使用了蛋白质编码和非编码两种靶标,以影响失调的途径,从而促进细胞毒性,增强免疫反应或对当前治疗敏感。基于病毒或非病毒系统的运载工具以及具有肿瘤归巢特性的细胞载体是基因治疗策略设计的关键部分。肿瘤细胞与非肿瘤细胞的不同行为激发了可以防止潜在的毒性相关作用的肿瘤选择性产物的产生,从而激发了载体工程学。在当前的审查中,提供了对不同目标,递送载体,临床前方法以及进行的临床试验的描述性更新的详细分析。此外,讨论了通过基因治疗策略治疗胰腺癌的未来可能性。

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