Abstract
Many advanced cancers resist therapeutic intervention. This process is fundamentally related to intra-tumor heterogeneity: multiple cell populations, each with different mutational and phenotypic signatures, coexist within a tumor and its metastatic nodes. Like species in an ecosystem, many cancer cell populations are intertwined in a complex network of ecological interactions. Most mathematical models of tumor ecology, however, cannot account for such phenotypic diversity nor are able to predict its consequences. Here we propose that the Generalized Lotka-Volterra model (GLV), a standard tool to describe complex, species-rich ecological communities, provides a suitable framework to describe the ecology of heterogeneous tumors. We develop a GLV model of tumor growth and discuss how its emerging properties, such as outgrowth and multistability, provide a new understanding of the disease. Additionally, we discuss potential extensions of the model and their application to three active areas of cancer research, namely phenotypic plasticity, the cancer-immune interplay and the resistance of metastatic tumors to treatment. Our work outlines a set of questions and a tentative road map for further research in cancer ecology.