Prospective molecular characterization of cancer has enabled physicians to define the genomic changes of each patient's tumor in real time and select personalized therapies based on these detailed portraits. Despite the promise of such an approach, previously unrecognized biological and therapeutic complexity is emerging. Here, we synthesize lessons learned and discuss the steps required to extend the benefits of genome-driven oncology, including proposing strategies for improved drug design, more nuanced patient selection, and optimized use of available therapies. Finally, we suggest ways that next-generation genome-driven clinical trials can evolve to accelerate our understanding of cancer biology and improve patient outcomes.

癌症的前瞻性分子表征使医生能够实时定义每个患者肿瘤的基因组变化，并根据这些详细的描述选择个性化治疗。尽管这种方法前景广阔，但之前未被认识到的生物学和治疗复杂性正在出现。在这里，我们总结经验教训，并讨论扩大基因组驱动肿瘤学益处所需的步骤，包括提出改进药物设计、更细致的患者选择和优化使用现有疗法的策略。最后，我们提出了下一代基因组驱动的临床试验的发展方向，以加速我们对癌症生物学的理解并改善患者的治疗结果。