Despite extensive research and improvements in understanding colorectal cancer (CRC), its metastatic form continues to pose a substantial challenge, primarily owing to limited therapeutic options and a poor prognosis. This Review addresses the emerging focus on metastatic CRC (mCRC), which has historically been under-studied compared with primary CRC despite its lethality. We delve into two crucial aspects: the molecular and cellular determinants facilitating CRC metastasis and the principles guiding the evolution of metastatic disease. Initially, we examine the genetic alterations integral to CRC metastasis, connecting them to clinically marked characteristics of advanced CRC. Subsequently, we scrutinize the role of cellular heterogeneity and plasticity in metastatic spread and therapy resistance. Finally, we explore how the tumour microenvironment influences metastatic disease, emphasizing the effect of stromal gene programmes and the immune context. The ongoing research in these fields holds immense importance, as its future implications are projected to revolutionize the treatment of patients with mCRC, hopefully offering a promising outlook for their survival.

尽管在了解结直肠癌 （CRC） 方面进行了广泛的研究和改进，但其转移形式仍然构成重大挑战，主要是由于治疗选择有限和预后不良。本综述讨论了对转移性 CRC （mCRC） 的新兴关注，尽管其致命性，但与原发性 CRC 相比，历史上对转移性 CRC 的研究不足。我们深入研究了两个关键方面：促进 CRC 转移的分子和细胞决定因素以及指导转移性疾病演变的原理。最初，我们检查了与 CRC 转移不可或缺的遗传改变，将它们与晚期 CRC 的临床特征联系起来。随后，我们仔细研究了细胞异质性和可塑性在转移扩散和治疗耐药中的作用。最后，我们探讨了肿瘤微环境如何影响转移性疾病，强调了基质基因程序和免疫环境的影响。这些领域正在进行的研究具有极其重要的意义，因为其未来影响预计将彻底改变 mCRC 患者的治疗，有望为他们的生存提供光明的前景。