SUMMARY In ecosystem modeling, the Allee effect describes a correlation between population size (number of members) and mean fitness (proliferation rate) of individuals. Increased proliferation with increased population size implies cooperative interactions. A contrasting principle in ecosystems is population “carrying capacity” which describes a decrease in growth rates with increasing population size, due to competition for limited resources. While the concept of carrying capacity has been studied in tumors (which may become limited in nutrients or oxygen), the Allee effect has been almost entirely overlooked. Allee effects are significant in small populations and thus may be critical to understanding the earliest steps in tumor iniation. To investigate the fundamental contribution of the Allee effect on tumor ecosystems requires the novel experimental designs and integration of quantitative experimental measurements with mathematical modeling. The overall goal of this project is to dissect the contribution of population size and cell-cell communication in a few selected, well-suited tumor cell lines through quantitative single-cell resolution, real-time monitoring of cell populations. Mathematical models of growth kinetics will show that the Allee effect and cell-cell communication has consequences on a single cancer cell’s decision to initiate a growing tumor or to stay dormant. These communication networks will be further mapped by identification of specific paracrine factors and receptors. Disruption of the communication network that establishes a proliferative tumor will be performed by targeting specific cell subpopulation interactions. Perturbations will include depletion of specific cell subtypes, manipulation of overall paracrine signaling, and blocking of specific ligand-receptor combinations on interacting species. These strategies may be novel tools to trigger tumor cell population collapse. Population-level effects in a nascent tumor population have not been quantitatively explored and may explain the phenomenon of critical thresholds and define a mechanistic role for intratumor heterogeneity. This project focuses on a fundamental generic principle that is broadly applicable in many contexts and thus could complement and enrich the modeling efforts of the cancer research community.