Understanding cancer evolution provides a clue to tackle therapeutic difficulties in colorectal cancer. In this review, together with related works, we will introduce a series of our studies, in which we constructed an evolutionary model of colorectal cancer by combining genomic analysis and mathematical modeling. In our model, multiple subclones were generated by driver mutation acquisition and subsequent clonal expansion in early-stage tumors. Among the subclones, the one obtaining driver copy number alterations is endowed with malignant potentials to constitute a late-stage tumor in which extensive intratumor heterogeneity is generated by the accumulation of neutral mutations. We will also discuss how to translate our understanding of cancer evolution to a solution to the problem related to therapeutic resistance: mathematical modeling suggests that relapse caused by acquired resistance could be suppressed by utilizing clonal competition between sensitive and resistant clones. Considering the current rate of technological development, modeling cancer evolution by combining genomic analysis and mathematical modeling will be an increasingly important approach for understanding and overcoming cancer.

了解癌症的演变为解决结直肠癌的治疗难题提供了线索。在这篇综述中，我们将结合相关工作介绍我们的一系列研究，其中我们结合基因组分析和数学建模构建了结直肠癌的进化模型。在我们的模型中，多个亚克隆是通过早期肿瘤中的驱动突变获取和随后的克隆扩增产生的。在亚克隆中，获得驱动拷贝数改变的亚克隆具有构成晚期肿瘤的恶性潜能，其中通过中性突变的积累产生广泛的瘤内异质性。我们还将讨论如何将我们对癌症进化的理解转化为与治疗耐药性相关的问题的解决方案：数学模型表明，可以通过利用敏感克隆和耐药克隆之间的克隆竞争来抑制由获得性耐药引起的复发。考虑到当前的技术发展速度，通过结合基因组分析和数学建模对癌症进化进行建模将成为理解和克服癌症的越来越重要的方法。