摘要
背景:几个基因偏差可能是引发致癌过程的原因之一。然而,肿瘤抑制基因的突变通常更多地与恶性疾病有关,其中p53是最受影响和研究最多的因素之一。p53参与了许多已知的细胞功能,包括DNA损伤修复、G1/S和G2/M期细胞周期阻滞和凋亡,是治疗癌症的重要靶点。目的:考虑到这些因素,以p53表达和调控为核心的基因治疗方法的发展似乎是一种很有前途的肿瘤治疗策略。结果:多项研究表明,用野生型p53表达质粒转染癌细胞可直接导致细胞凋亡和/或生长停滞,提示肿瘤治疗的基因治疗方法是通过重新建立正常的p53表达水平和功能来实现的。到目前为止,已经完成了几项临床研究,使用携带p53基因的病毒和非病毒载体分离或与其他治疗药物联合使用,市场上已经有基于这种基因的治疗方法。结论:本文综述了P53的不同传递和(或)靶向方法,以及应用不同策略所取得的主要疗效。最后,介绍了目前正在进行的治疗方法,并重点介绍了联合应用基因治疗载体和化疗或放射治疗的组合疗法,以显示出更大的治疗潜力。
关键词: p53,凋亡,非病毒载体,基因治疗。
图形摘要
Current Drug Targets
Title:p53 as the Focus of Gene Therapy: Past, Present and Future
Volume: 19 Issue: 15
关键词: p53,凋亡,非病毒载体,基因治疗。
摘要: Background: Several gene deviations can be responsible for triggering oncogenic processes. However, mutations in tumour suppressor genes are usually more associated to malignant diseases, with p53 being one of the most affected and studied element. p53 is implicated in a number of known cellular functions, including DNA damage repair, cell cycle arrest in G1/S and G2/M and apoptosis, being an interesting target for cancer treatment.
Objective: Considering these facts, the development of gene therapy approaches focused on p53 expression and regulation seems to be a promising strategy for cancer therapy.
Results: Several studies have shown that transfection of cancer cells with wild-type p53 expressing plasmids could directly drive cells into apoptosis and/or growth arrest, suggesting that a gene therapy approach for cancer treatment can be based on the re-establishment of the normal p53 expression levels and function. Up until now, several clinical research studies using viral and non-viral vectors delivering p53 genes, isolated or combined with other therapeutic agents, have been accomplished and there are already in the market, therapies based on the use of this gene.
Conclusion: This review summarizes the different methods used to deliver and/or target the p53 as well as the main results of therapeutic effect obtained with the different strategies applied. Finally, the ongoing approaches are described, also focusing on the combinatorial therapeutics to show increased therapeutic potential of combining gene therapy vectors with chemo or radiotherapy.
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p53 as the Focus of Gene Therapy: Past, Present and Future, Current Drug Targets 2018; 19 (15) . https://dx.doi.org/10.2174/1389450119666180115165447
DOI https://dx.doi.org/10.2174/1389450119666180115165447 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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