Adaptive Therapy and the Cost of Drug-Resistant Mutants.

Abstract

The concept of adaptive cancer therapy proposes that the use of drugs at less than maximum tolerated dose can provide clinical benefits by allowing persisting drug-sensitive cells to competitively suppress drug-resistant cells; this can delay the outgrowth of these cell clones. The adaptive therapy concept has been developed with mathematical models and has subsequently been explored in clinical trials with promising results. In studies performed so far, a fitness cost of drug-resistant cells has been invoked for this treatment approach to be beneficial. In new work, it is shown that a clinical benefit can be achieved even in the absence of a fitness cost for resistant cells, which broadens the applicability of adaptive therapy.<i>See related article by Strobl et al., p. 1135</i>.