Cytotoxic therapy induced shifts in the cost-to-benefit ratio of high ploidy

Energetic costs of DNA content levels required for >75% SCNA load do not, in the absence of cytotoxic therapy, justify the masking benefits they bring. We integrate single cell sequencing with imaging and mathematical modeling of heterogeneous populations evolving through chromosome missegregations to explain observed SCNA landscapes and missegregation tolerances, and to predict effective cytotoxic therapy doses. We evaluate Oxygen, Phosphate and Glucose as rate-limiting substrates of dNTP synthesis of co-evolving subpopulations in stomach and brain tissue environments.