癌症靶向治疗的新趋势

靶向性是癌症治疗的关键所在,新的治疗方案必须在特异性作用于肿瘤的同时降低对正常细胞的损伤,目前已取得了许多成果:1)肿瘤的靶向基因-病毒治疗结合了基因治疗和病毒治疗的各自优势。所用的病毒载体具有特异性靶向肿瘤的作用并在肿瘤细胞中大量复制和高效表达抗癌基因,如果用2个特异性启动子严格控制病毒只在肿瘤中表达,并加上2个有协同效应的抗癌基因即可达到极好的抗癌效果。2)在抗体治疗方面,运用第1代腺病毒高效表达Her-ceptin或是Rituxan抗体基因已取得成功,它可以大大地降低目前昂贵的抗体治疗费用。3)RNA干扰技术可以沉默致病基因,选用质粒或是病毒做载体可以达到长期及高效的基因沉默效果。4)具有自我更新能力的肿瘤干细胞是肿瘤复发的关键。5)人们也逐渐意识到肿瘤的形成过程是癌细胞与基质细胞相互作用的结果,以肿瘤基质为靶标的药物也显示出了良好的效果。6)针对蛋白酪氨酸激酶或是抗凋亡蛋白而研制的小分子靶向药物也在肿瘤分子治疗上取得了成功。7)纳米技术正以其独特性而引起广泛关注。总之,在众多新型治疗方案研发的同时,我们必须认识到仅仅靠一种方法是难以成功根治肿瘤的,各种靶向治疗方案之间的相互结合将成为肿瘤治疗的主攻方向。

New trends of targeting cancer therapy

The key point in cancer therapy is targeting, i.e. the new therapeutic agents should specifically act on tumor cells meanwhile reducing the cytoxicity to the normal cells. There are some new trends in the design of therapeusis and several of them may be promising strategies. Targeting Gene-Virotherapy of Cancer is the combination of gene therapy and oncolytic virotherapy. This viral vector carrying therapeutic gene is under the control of one tumor-specific promoter to obtain restricted replication and expression of gene in tumor cells. Using two tandem promoters and two compensative/synergic genes will achieve better curative effect. To antibody therapy, large quantitive expression of Herceptin or Rituxan by first-generation adenoviral vector will reduce the expensive fee of antibody therapy. RNAi technology-directed gene silencing might allow the silencing of genes that are pathogenic to the host organism. Plasmid vectors or viral vectors have been used as siRNA delivery systems to obtain stable and efficient silencing. Cancer cells may include cancer stem cells with indefinite potential for self-renewal that drive tumorigenesis, studies of cancer stem cells will ultimately yield new approaches to fight cancer. Recently, tumor progression has been recognized as the product of an evolving crosstalk between different cell types within the tumor and its surrounding supporting tissue or tumor stroma. The development of microenvironment-based therapies is now underway. Therapeutic drugs have driven the recent success in the field of molecular cancer therapeutics and many of them target the protein tyrosine kinase or the antiapoptotic proteins. The nanometer technology has received particular attention based on its potential therapeutic effect on tumor cells. When developing new therapies, we need to keep in mind that targeting tumor cells just by one strategy is not likely to be successful. Therefore, the aim should be to combine the strategies.