Despite standardization of multimodal treatment and approval of several targeted drugs for resectable, non-metastatic cancer (M0 patients), intrinsic and acquired resistance and relapse rates remain high, even in early-stage aggressive tumors. Genome analysis could overcome these unmet needs. Our comprehensive review underlines the controversy on stable or spatiotemporally evolving clones as well as promising yet inconclusive data on genome-based biomarkers and drug development. We propose clinicogenomic trials in M0 patients for the validation of intratumor heterogeneity (ITH), circulating genomic subclones (cGSs) and intra-patient genomic heterogeneity (IPGH) as biomarkers and simultaneous discovery of novel oncotargets. This evidence-based strategy highlights the coming of precision surgical oncology with a future perspective of understanding and disrupting deregulated transcriptional networks.

尽管对多模式治疗进行了标准化并批准了可切除的，非转移性癌症（M0患者）的几种靶向药物，但即使在早期侵袭性肿瘤中，内在和获得性耐药和复发率仍然很高。基因组分析可以克服这些未满足的需求。我们的全面审查强调了关于稳定或时空进化的克隆的争议，以及有关基于基因组的生物标志物和药物开发的有希望但尚无定论的数据。我们建议在M0患者中进行临床基因组学试验，以验证肿瘤内异质性（ITH），循环基因组亚克隆（cGSs）和患者内基因组异质性（IPGH）作为生物标志物并同时发现新型肿瘤靶标。