Ovarian Cancer Research Center, Translational Research Center, University of Pennsylvania, Philadelphia, PA, USA.
Bioimpacts. 2012;2(3):127-43. doi: 10.5681/bi.2012.025. Epub 2012 Sep 22.
Of the cancer gene therapy approaches, gene silencing, suicide/apoptosis inducing gene therapy, immunogene therapy and targeted gene therapy are deemed to sub-stantially control the biological consequences of genomic changes in cancerous cells. Thus, a large number of clinical trials have been conducted against various malignancies. In this review, we will discuss recent translational progresses of gene and cell therapy of cancer.
Essential information on gene therapy of cancer were reviewed and discussed towards their clinical translations.
Gene transfer has been rigorously studied in vitro and in vivo, in which some of these gene therapy endeavours have been carried on towards translational investigations and clinical applications. About 65% of gene therapy trials are related to cancer therapy. Some of these trials have been combined with cell therapy to produce personalized medicines such as Sipuleucel-T (Provenge®, marketed by Dendreon, USA) for the treatment of asymptomatic/minimally symptomatic metastatic hormone-refractory prostate cancer.
Translational approach links two diverse boundaries of basic and clinical researches. For successful translation of geno-medicines into clinical applications, it is essential 1) to have the guidelines and standard operating procedures for development and application of the genomedicines specific to clinically relevant biomarker(s); 2) to conduct necessary animal experimental studies to show the "proof of concept" for the proposed genomedicines; 3) to perform an initial clinical investigation; and 4) to initiate extensive clinical trials to address all necessary requirements. In short, translational researches need to be refined to accelerate the geno-medicine development and clinical applications.
在癌症基因治疗方法中,基因沉默、自杀/凋亡诱导基因治疗、免疫基因治疗和靶向基因治疗被认为可以有效地控制癌细胞基因组变化的生物学后果。因此,已经针对各种恶性肿瘤开展了大量的临床试验。在这篇综述中,我们将讨论癌症基因和细胞治疗的最新转化进展。
对癌症基因治疗的重要信息进行了综述和讨论,以期将其转化为临床应用。
基因转移已在体外和体内进行了严格的研究,其中一些基因治疗努力已朝着转化研究和临床应用方向进行。约 65%的基因治疗试验与癌症治疗有关。其中一些试验已与细胞治疗相结合,以产生个性化药物,如 Sipuleucel-T(Provenge®,由美国 Dendreon 公司销售),用于治疗无症状/轻度症状转移性激素难治性前列腺癌。
转化方法连接了基础研究和临床研究的两个不同边界。为了将基因药物成功转化为临床应用,必须:1)制定针对临床相关生物标志物的基因药物开发和应用的指南和标准操作程序;2)进行必要的动物实验研究,以证明所提出的基因药物的“概念验证”;3)进行初步的临床研究;4)启动广泛的临床试验,以满足所有必要的要求。简而言之,需要对转化研究进行细化,以加速基因药物的开发和临床应用。