Abstract
Integration of ecological and evolutionary features has begun to understand the interplay of tumor heterogeneity, microenvironment, and metastatic potential. Developing a theoretical framework is intrinsic to deciphering tumors' tremendous spatial and longitudinal genetic variation patterns in patients. Here, we propose that tumors can be considered evolutionary island-like ecosystems, that is, isolated systems that undergo evolutionary and spatiotemporal dynamic processes that shape tumor microenvironments and drive the migration of cancer cells. We examine attributes of insular systems and causes of insularity, such as physical distance and connectivity. These properties modulate migration rates of cancer cells through processes causing spatial and temporal isolation of the organs and tissues functioning as a supply of cancer cells for new colonizations. We discuss hypotheses, predictions, and limitations of tumors as islands analogy. We present emerging evidence of tumor insularity in different cancer types and discuss their relevance to the islands model. We suggest that the engagement of tumor insularity into conceptual and mathematical models holds promise to illuminate cancer evolution, tumor heterogeneity, and metastatic potential of cells.