Metastasis is the spread of tumor cells through blood or the lymph system to form new tumors in otherwise healthy organs. Circulating tumor cells (CTCs) in the bloodstream often form clusters of CTCs. Some evidence suggests that when CTCs form clusters, they become more resistant to the body’s immune responses. However, other evidence suggests that cluster formation does not significantly affect metastasis. This CAREER project will use computer modeling and artificial intelligence (AI) to examine CTC clusters in the circulatory system. Simulations will describe how CTC clusters move through the bloodstream, how they respond to challenges from the immune system, and how they differ in different types of cancer. AI will be used to analyze large data sets, find patterns, and predict the behavior of CTC clusters. The models will be integrated into user-friendly, open-source software. The project will develop interactive K-12 workshops that teach students about the structure of cells and, for advanced students, how to model them. Research findings will be integrated into courses at the University of Alabama in Huntsville. The project outcomes may lead to better ways to diagnose and treat cancer, especially by targeting CTC clusters. This CAREER project will provide insight into outstanding questions on CTC clusters from their entry to the circulatory system to their exit at a secondary location. The project will use a three-component computational modeling framework built on a comprehensive and continuously updated set of experimental data. The first component of the framework will be a new model of CTC cluster dynamics that combines mechanistic modeling of the clusters with environmental cues, interactions with other cells, intercellular communication, and the physiological state of clustered CTCs. The second component will result in a detailed kinetic model of CTC cluster metabolism that integrates multiple experimental datasets through advanced statistical meth