Interplay between mutational pathway and drug gradient controls time to evolution of drug resistance

Details Interplay between mutational pathway and drug gradient controls time to evolution of drug resistance Interplay between mutational pathway and drug gradient controls time to evolution of drug resistance

2012-02-24

arxiv.org/abs/1202.5431v3

Biology

Quantitative Biology

Populations and Evolution

5 pages, 3 figures

Scientific paper

Drug gradients are believed to play an important role in the evolution of drug resistance, from antibiotics to cancer. We use a statistical physics model to study the evolution of a population of malignant cells exposed to drug gradients, where drug resistance emerges via multiple mutations. We show that a non-uniform drug concentration can strongly accelerate the emergence of resistance when the mutational pathway involves a long sequence of mutants with increasing resistance, but slows it down if the pathway is short or crosses a fitness valley. These predictions can be verified experimentally, and have the potential to improve strategies to combat the emergence of resistance.

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