Duursma Anja M, Agami Reuven
Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Semin Cancer Biol. 2003 Aug;13(4):267-73. doi: 10.1016/s1044-579x(03)00040-3.
Activating point mutations of the small GTPase Ras are present in about 30% of all human tumors. Constitutively active Ras induces growth factor independent cell proliferation and cell survival. Oncogenic Ras appears to be essential for tumor progression and maintenance. Several therapeutic agents have been developed to inhibit Ras, such as FTIs and antisense oligonucleotides. A new tool for blocking oncogenes in cancer cells has emerged with the discovery that RNA interference can specifically silence expression of endogenous human genes. The therapeutic potential of a RNAi-mediating vector was recently demonstrated by the stable suppression of oncogenic K-Ras in tumor cells.
小GTP酶Ras的激活点突变存在于约30%的人类肿瘤中。持续激活的Ras可诱导不依赖生长因子的细胞增殖和细胞存活。致癌性Ras似乎对肿瘤进展和维持至关重要。已经开发了几种抑制Ras的治疗药物,如法尼基转移酶抑制剂(FTIs)和反义寡核苷酸。随着RNA干扰可特异性沉默内源性人类基因表达这一发现的出现,一种用于阻断癌细胞中癌基因的新工具应运而生。最近,通过在肿瘤细胞中稳定抑制致癌性K-Ras,证明了RNA干扰介导载体的治疗潜力。