Dienstmann Rodrigo, Jang In Sock, Bot Brian, Friend Stephen, Guinney Justin
Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Cancer Discov. 2015 Feb;5(2):118-23. doi: 10.1158/2159-8290.CD-14-1118.
Comprehensive genomic profiling is expected to revolutionize cancer therapy. In this Prospective, we present the prevalence of mutations and copy-number alterations with predictive associations across solid tumors at different levels of stringency for gene-drug targetability. More than 90% of The Cancer Genome Atlas samples have potentially targetable alterations, the majority with multiple events, illustrating the challenges for treatment prioritization given the complexity of the genomic landscape. Nearly 80% of the variants in rarely mutated oncogenes are of uncertain functional significance, reflecting the gap in our understanding of the relevance of many alterations potentially linked to therapeutic actions. Access to targeted agents in early clinical trials could affect treatment decision in 75% of patients with cancer. Prospective implementation of large-scale molecular profiling and standardized reports of predictive biomarkers are fundamental steps for making precision cancer medicine a reality.
全面基因组分析有望彻底改变癌症治疗。在本前瞻性研究中,我们展示了不同严格程度下实体瘤中具有预测关联的突变和拷贝数改变的发生率,这些关联涉及基因-药物靶向性。超过90%的癌症基因组图谱样本具有潜在可靶向改变,大多数存在多个事件,这表明鉴于基因组格局的复杂性,在确定治疗优先级方面存在挑战。罕见突变癌基因中近80%的变异功能意义不确定,这反映出我们在理解许多可能与治疗作用相关的改变的相关性方面存在差距。在早期临床试验中使用靶向药物可能会影响75%癌症患者的治疗决策。前瞻性实施大规模分子分析和预测性生物标志物的标准化报告是使精准癌症医学成为现实的基本步骤。