Department of Cell Regulation, Genentech Inc, South San Francisco, CA, USA.
EMBO Mol Med. 2009 Sep;1(6-7):297-9. doi: 10.1002/emmm.200900044.
While the use of synthetic lethality has been around for decades in model organism studies, it has only recently been applied to cancer therapy and judging by recent results, with great success. Following on a recent paper that demonstrates the clinical application of this strategy (Fong et al, 2009), Chris Lord and Alan Ashworth further explore the approach and show that poly(ADP-ribose) polymerase (PARP) inhibitors such as Olaparib can selectively target cancer cells defective in phosphatase and tensin homologue (PTEN, Mendes-Pereira et al, 2009) and that methotrexate is selectively lethal to MutS-homologue-2 (MSH2)-deficient tumour cells (Martin et al, 2009).
虽然合成致死在模式生物研究中已经存在了几十年,但直到最近才被应用于癌症治疗,而且从最近的结果来看,取得了巨大的成功。继最近一篇证明该策略临床应用的论文之后(Fong 等人,2009 年),Chris Lord 和 Alan Ashworth 进一步探讨了这种方法,并表明聚(ADP-核糖)聚合酶(PARP)抑制剂,如奥拉帕尼,可以选择性地靶向磷酸酶和张力蛋白同源物(PTEN,Mendes-Pereira 等人,2009 年)缺陷的癌细胞,并且甲氨蝶呤对 MutS 同源物-2(MSH2)缺陷的肿瘤细胞具有选择性致死作用(Martin 等人,2009 年)。