Colorectal cancer (CRC) has a global burden of disease. Our current understanding of CRC has progressed from initial discoveries which focused on the stepwise accumulation of key driver mutations, as encapsulated in the Vogelstein model, to one in which marked heterogeneity leads to a complex interplay between clonal populations. Current evidence suggests that an initial explosion, or “Big Bang”, of genetic diversity is followed by a period of neutral dynamics. A thorough understanding of this interplay between clonal populations during neutral evolution gives insights into the roles in which driver genes may participate in the progress from normal colonic epithelium to adenoma and carcinoma. Recent advances have focused not only on genetics, transcriptomics, and proteomics but have also investigated the ecological and evolutionary processes which transform normal cells into cancer. This review first describes the role which driver mutations play in the Vogelstein model and subsequently demonstrates the evidence which supports a more complex model. This article also aims to underscore the significance of tumour heterogeneity and diverse clonal populations in cancer progression.

结直肠癌 (CRC) 是全球疾病负担。我们目前对 CRC 的理解已经从最初的发现进展到关注关键驱动突变的逐步积累，如封装在 Vogelstein 模型中，到其中显着的异质性导致克隆种群之间复杂的相互作用。目前的证据表明，遗传多样性的最初爆炸或“大爆炸”之后是一段中性动态时期。对中性进化过程中克隆种群之间的这种相互作用的透彻理解可以深入了解驱动基因可能参与从正常结肠上皮到腺瘤和癌的进程。最近的进展不仅集中在遗传学、转录组学、和蛋白质组学，但也研究了将正常细胞转化为癌症的生态和进化过程。这篇综述首先描述了驱动突变在 Vogelstein 模型中的作用，随后展示了支持更复杂模型的证据。本文还旨在强调肿瘤异质性和不同克隆群体在癌症进展中的重要性。