Modeling tumors as complex ecosystems.

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 metastases. Like species in an ecosystem, cancer populations are intertwined in a complex network of ecological interactions. Most mathematical models of tumor ecology, however, cannot account for such phenotypic diversity 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 model the ecology of heterogeneous tumors. We develop a GLV model of tumor growth and discuss how its emerging properties provide a new understanding of the disease. We discuss potential extensions of the model and their application to phenotypic plasticity, cancer-immune interactions, and metastatic growth. Our work outlines a set of questions and a road map for further research in cancer ecology.