The clonal evolution model of cancer was developed in the 1950s–1970s and became central to cancer biology in the twenty-first century, largely through studies of cancer genetics. Although it has proven its worth, its structure has been challenged by observations of phenotypic plasticity, non-genetic forms of inheritance, non-genetic determinants of clone fitness and non-tree-like transmission of genes. There is even confusion about the definition of a clone, which we aim to resolve. The performance and value of the clonal evolution model depends on the empirical extent to which evolutionary processes are involved in cancer, and on its theoretical ability to account for those evolutionary processes. Here, we identify limits in the theoretical performance of the clonal evolution model and provide solutions to overcome those limits. Although we do not claim that clonal evolution can explain everything about cancer, we show how many of the complexities that have been identified in the dynamics of cancer can be integrated into the model to improve our current understanding of cancer.

癌症的克隆进化模型是在 1950 年代至 1970 年代开发的，并主要通过癌症遗传学研究成为 21 世纪癌症生物学的核心。尽管它已经证明了它的价值，但它的结构受到了对表型可塑性的观察、非遗传形式的遗传、克隆适应性的非遗传决定因素和基因的非树状传递的挑战。甚至对克隆的定义也存在混淆，我们的目标是解决这个问题。克隆进化模型的性能和价值取决于进化过程与癌症相关的实证程度，以及其解释这些进化过程的理论能力。在这里，我们确定了克隆进化模型理论性能的极限，并提供了克服这些极限的解决方案。虽然我们并不声称克隆进化可以解释关于癌症的一切，但我们展示了在癌症动力学中已经确定的许多复杂性可以整合到模型中，以提高我们目前对癌症的理解。