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Precision medicine relies on the idea that, for a particular targeted agent, only a subpopulation of patients is sensitive to it and thus may benefit from it therapeutically. In practice, it is often assumed based on preclinical data that a treatment-sensitive subpopulation is known, and moreover that the agent is substantively efficacious in that subpopulation. Due to important differences between preclinical settings and human biology, however, data from patients treated with a new targeted agent often show that one or both of these ass