Abstract
Many cancers resist therapeutic intervention. This is fundamentally related to intratumor heterogeneity:multiple cell populations, each with different phenotypic signatures, coexist within a tumor and its metas-tases. Like species in an ecosystem, cancer populations are intertwined in a complex network of ecologicalinteractions. Most mathematical models of tumor ecology, however, cannot account for such phenotypicdiversity or predict its consequences. Here, we propose that the generalized Lotka-Volterra model (GLV),a standard tool to describe species-rich ecological communities, provides a suitable framework to modelthe ecology of heterogeneous tumors. We develop a GLV model of tumor growth and discuss how itsemerging properties provide a new understanding of the disease. We discuss potential extensions ofthe model and their application to phenotypic plasticity, cancer-immune interactions, and metastaticgrowth. Our work outlines a set of questions and a road map for further research in cancer ecology.