Predator–Prey Model for Simulating the Genetic Carcinogenicity of Aggressive Toxicant‐Related Cancer

The mechanism of how toxicant exposure leads to aggressive tumors remains unresolved. A genetic-based hypothesis predicts that under stress, the transcription of growth-related genes will be inhibited by the activation of mitogenic pathways, redirecting energy toward stress response and increasing survival. This hypothesis fails to explain why epidemiological data suggest that growth and stress response are activated, as patients exposed to toxicants exhibit more aggressive growth than nonexposed individuals. This co-occurrence requires increased energy availability to prevent the activation of mitogenic pathways, as seen in the Warburg effect. We hypothesize that if pollutant effects cease, it might drive aggressive cancer, as excess energy that is no longer used for stress response can fuel rapid growth. We model this allocation between growth and stress response as a trophic competition using the Lotka-Volterra equations and using as input RNA-Seq data from growth- and stress-related genes obtained from cancer cells exposed to copper, cadmium, and carboplatin. Our findings suggest that the energy allocation to growth and its rate of allocation is higher in exposed than nonexposed tumors and results in overgrowth in unexposed cells. This study helps to understand how certain scenarios, such as partial or total cessation of exposure, in toxicant-related cancer can drive cancer aggressiveness.