Biroccio Annamaria, Leonetti Carlo, Zupi Gabriella
Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.
Oncogene. 2003 Sep 29;22(42):6579-88. doi: 10.1038/sj.onc.1206812.
The current direction in cancer research is rational drug design, which is based on the evidence that transformed cells are characterized by alterations of genes devoted to the regulation of both cell proliferation and apoptosis. A variety of approaches have been carried out to develop new agents selective for cancer cells. Among these, antisense oligonucleotides (ASOs) are one of such class of new agents able to inhibit specifically the synthesis of a particular cancer-associated protein by binding to protein-encoding RNA, thereby preventing RNA function. In the past decade, several ASOs have been developed and tested in preclinical and clinical studies. Many have shown convincing in vitro reduction in target gene expression and promising activity against a wide variety of tumors. However, because of the multigenic alterations of tumors, the use of ASOs as single agents does not seem to be effective in the treatment of malignancies. Antisense therapy that interferes with signaling pathways involved in cell proliferation and apoptosis are particularly promising in combination with conventional anticancer treatment. An overview of the progress of ASOs used in combination therapy is provided.
当前癌症研究的方向是合理药物设计，其依据是转化细胞的特征在于参与细胞增殖和凋亡调节的基因发生改变。已经开展了多种方法来开发对癌细胞具有选择性的新药物。其中，反义寡核苷酸（ASO）是这类新药物之一，它能够通过与编码蛋白质的RNA结合来特异性抑制特定癌症相关蛋白的合成，从而阻止RNA发挥功能。在过去十年中，已经开发了几种ASO并在临床前和临床研究中进行了测试。许多ASO在体外显示出令人信服的靶基因表达降低以及对多种肿瘤具有有前景的活性。然而，由于肿瘤的多基因改变，将ASO作为单一药物使用似乎在恶性肿瘤治疗中并不有效。与传统抗癌治疗联合使用时，干扰参与细胞增殖和凋亡的信号通路的反义疗法特别有前景。本文提供了联合治疗中使用的ASO的进展概述。
