A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity

A new model of tumour evolution is presented to explain how short-range migration and cell turnover within the tumour can provide the basic environment of rapid cell mixing, allowing even a small selective advantage to dominate the mass within relevant time frames. A 3D model of solid tumour evolution Although a large tumour can contain billions of cells, these masses are highly homogeneous. A mass of normal cells of that size would be expected to be genetically diverse due to the slow collection of modest random mutations following cell divisions, raising the question of how cancers can maintain homogeneity at such a scale. Here Martin Nowak and colleagues propose a model of tumour evolution that explains how short-range migration and cell turnover within the tumour can provide an environment of rapid cell mixing that would allow even a small selective advantage to dominate the cell mass within a relevant time frame. Most cancers in humans are large, measuring centimetres in diameter, and composed of many billions of cells 1 . An equivalent mass of normal cells would be highly heterogeneous as a result of the mutations that occur during each cell division. What is remarkable about cancers is that virtually every neoplastic cell within a large tumour often contains the same core set of genetic alterations, with heterogeneity confined to mutations that emerge late during tumour growth 2 , 3 , 4 , 5 . How such alterations expand within the spatially constrained three-dimensional architecture of a tumour, and come to dominate a large, pre-existing lesion, has been unclear. Here we describe a model for tumour evolution that shows how short-range dispersal and cell turnover can account for rapid cell mixing inside the tumour. We show that even a small selective advantage of a single cell within a large tumour allows the descendants of that cell to replace the precursor mass in a clinically relevant time frame. We also demonstrate that the same mechanisms can be responsible for the rapid onset of resistance to chemotherapy. Our model not only provides insights into spatial and temporal aspects of tumour growth, but also suggests that targeting short-range cellular migratory activity could have marked effects on tumour growth rates.