Varmus H, Pao W, Politi K, Podsypanina K, Du Y-C N
Program in Cancer Biology and Genetics, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cold Spring Harb Symp Quant Biol. 2005;70:1-9. doi: 10.1101/sqb.2005.70.039.
Mutations of proto-oncogenes are common events in the pathogenesis of cancers, as shown in a wide range of studies during the 30 years since the discovery of these genes. The benefits of novel therapies that target the products of mutant alleles in human cancers, and the demonstrated dependence of cancers in mouse models on continued expression of initiating oncogenes, are especially promising signs that revolutionary improvements in cancer care are possible. Full realization of the promise of targeted therapies, however, will require better definitions of the genotypes of human cancers, new approaches to interrupt the biochemical consequences of oncogenic mutations, and a greater understanding of drug resistance and tumor progression. In this paper, we summarize recent efforts toward these goals in our laboratory and others.
原癌基因的突变是癌症发病机制中的常见事件，自这些基因被发现后的30年里，众多研究均表明了这一点。针对人类癌症中突变等位基因产物的新型疗法所带来的益处，以及在小鼠模型中证实的癌症对起始癌基因持续表达的依赖性，都是癌症治疗可能取得革命性进展的特别有前景的迹象。然而，要充分实现靶向治疗的前景，将需要更明确地定义人类癌症的基因型、中断致癌突变生化后果的新方法，以及对耐药性和肿瘤进展有更深入的了解。在本文中，我们总结了我们实验室及其他实验室为实现这些目标所做的最新努力。
