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Explore how spatial organization fundamentally shapes cellular evolution and selection in tumor architecture through this 34-minute conference talk. Examine spatially explicit computational modeling approaches for cellular dynamics and evolution, focusing on the relationship between continuous-space agent-based models and coarse-grained deme models that enable analytical tractability. Investigate mutant evolution in spatially structured populations by analyzing expanding populations across different dimensions and studying mutant invasion at steady state, relevant for both non-neoplastic tissue and tumors in growth plateau phases during multi-step carcinogenesis. Discover how spatial structure can reverse conventional selection principles, where mutants with increased reproductive output may experience negative selection when multiple kinetic parameters change simultaneously, such as concurrent increases in both division and death rates. Learn how this challenges the fundamental assumption that higher reproductive output always confers evolutionary advantage. Gain insights into the implications for driver mutation selection, tumor progression, and therapeutic resistance, while understanding how spatial population structure can fundamentally alter evolutionary principles in unexpected ways, deepening comprehension of tumor cell emergence during progression and therapy.
