289

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Issue 289: Drug-resistant and drug-sensitive cancer cells respond to different concentrations of drugs in different ways. For instance, resistant cells may grow slower than sensitive cells when drug levels are low - we call this a cost to drug resistance. When considering how a single tumor may have multiple subtypes of cells with varying levels of resistance existing simultaneously, understanding how these different subtypes are selected during therapy becomes complicated. Furthermore, studies of drug diffusion in tumors have shown that the drug concentration may drop off steeply as distance from a blood vessel increases. Here, we sought to understand how different patterns of drug diffusion interact with variable drug sensitivities among different tumor subtypes. Using agent-based modeling, we simulated tumor evolution with different rates of drug diffusion. The top row of the picture shows the different drug diffusion profiles, with the rate of diffusion increasing from left to right. The bottom row shows multiple replicates of simulated tumors responding to the drug concentration profile above. This work suggests that drug diffusion may be a driver of tumor heterogeneity, potentially contributing to treatment failure.