Re-Evaluating Clonal Dominance in Cancer Evolution

Tumours are composed of genetically heterogeneous subclones which may diverge early during tumour growth. However, our strategies for treating and assessing outcome for patients are overwhelmingly based upon the classical linear paradigm for cancer evolution. Increasing numbers of studies are finding that minor subclones can determine clinical disease course, and that temporal and spatial heterogeneity needs to be considered in disease management. In this article we review evidence for cancer clonal heterogeneity, evaluating the importance of tumour subclones and their growth through both Darwinian and neutral evolution. Major shifts in current clinical practice and trial designs, aimed at understanding cancer evolution on a patient-by-patient basis, may be necessary to achieve more successful treatment of heterogeneous metastatic disease.