Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC 27599, USA.
Science. 2013 Mar 29;339(6127):1563-6. doi: 10.1126/science.1234139.
The past decade has brought together substantial advances in human genome analysis and a maturation of understanding of tumor biology. Although there is much progress still to be made, there are now several prominent examples in which tumor-associated somatic mutations have been used to identify cellular signaling pathways in tumors. This in turn has led to the development of targeted therapies, with somatic mutations serving as genomic predictors of tumor response and providing new leads for drug development. There is also a realization that germline DNA variants can help optimize cancer drug dosing and predict the susceptibility of patients to the adverse side effects of these drugs-knowledge that ultimately can be used to improve the benefit:risk ratio of cancer treatment for individual patients.
过去十年，人类基因组分析取得了重大进展，对肿瘤生物学的认识也日趋成熟。尽管仍有许多工作要做，但现在已经有一些突出的例子，其中肿瘤相关的体细胞突变被用于鉴定肿瘤中的细胞信号通路。这反过来又导致了靶向治疗的发展，体细胞突变作为肿瘤反应的基因组预测因子，并为药物开发提供了新的线索。人们也意识到种系 DNA 变体可以帮助优化癌症药物剂量，并预测患者对这些药物不良反应的易感性——这些知识最终可以用于提高癌症治疗对个体患者的获益风险比。
