Cancer is an evolutionary process fueled by genetic or epigenetic alterations in the genome. Understanding the evolutionary dynamics that are operative at different stages of tumor progression might inform effective strategies in early detection, diagnosis, and treatment of cancer. However, our understanding on the dynamics of tumor evolution through time is very limited since it is usually impossible to sample patient tumors repeatedly. The recent advances in in vitro 3D organoid culture technologies have opened new avenues for the development of more realistic human cancer models that mimic many in vivo biological characteristics in human tumors. Here, we review recent progresses and challenges in cancer genomic evolution studies and advantages of using tumor organoids to study cancer evolution. We propose to establish an experimental evolution model based on continuous passages of patient-derived organoids and longitudinal sampling to study clonal dynamics and evolutionary patterns over time. Development and integration of population genetic theories and computational models into time-course genomic data in tumor organoids will help to pinpoint the key cellular mechanisms underlying cancer evolutionary dynamics, thus providing novel insights on therapeutic strategies for highly dynamic and heterogeneous tumors.

癌症是由基因组遗传或表观遗传改变推动的进化过程。了解肿瘤进展不同阶段的进化动力学可能为癌症早期检测、诊断和治疗的有效策略提供信息。然而，我们对肿瘤随时间演变动态的理解非常有限，因为通常不可能重复对患者肿瘤进行采样。体外3D 类器官培养技术的最新进展为开发更真实的人类癌症模型开辟了新途径，这些模型可以模仿人类肿瘤的许多体内生物学特征。在这里，我们回顾了癌症基因组进化研究的最新进展和挑战，以及使用肿瘤类器官研究癌症进化的优势。我们建议建立一个基于患者源性类器官的连续传代和纵向采样的实验进化模型，以研究克隆动态和随时间的进化模式。将群体遗传理论和计算模型发展并整合到肿瘤类器官的时程基因组数据中，将有助于查明癌症进化动力学的关键细胞机制，从而为高度动态和异质性肿瘤的治疗策略提供新的见解。