Abstract
Cancer stem cells (CSCs) proactively remodel their microenvironment to maintain a supportive niche. Viewed through the lens of an ecosystem, numerous tumor components have multi-directional interactions involving CSCs, supporting the complexity of tumors to maintain growth in a dynamic host. In this Perspective, we discuss how CSCs are active architects of their microenvironment and drive interactions with other tumor components, such as immune cells, cancer-associated fibroblasts and differentiated cells, blood vessels, and other extracellular cues to engineer a sustainable niche. We also highlight considerations for modeling this dynamic tumor ecology and discuss potential therapeutic strategies for targeting these multifaceted interactions.