Conditional success of adaptive therapy: the role of treatment-pausing thresholds revealed by mathematical modeling

Adaptive therapy (AT) improves cancer treatment by controlling the competition between sensitive and resistant cells via treatment holidays. This study highlights the critical role of treatment-pausing thresholds in AT for tumors composed of drug-sensitive and resistant cells. Using a Lotka-Volterra model, the research compares AT with maximum tolerated dose therapy and intermittent therapy, showing that AT’s success largely depends on the threshold at which treatment is paused and resumed, as well as the competition between sensitive and resistant cells. Three scenarios of comparison between AT and others are identified: uniform-decline, conditionalimprove, and uniform-improve, illustrating that optimizing the treatment-pausing threshold is crucial for AT effectiveness. Tumor composition, including initial tumor burden and the proportion of resistant cells, influences outcomes. Adjusting threshold values enables AT to suppress resistant subclones, preserving sensitive cells, ultimately improving progression-free survival. These findings underscore the importance of personalized strategies for cancer management and enhancing long-term therapeutic outcomes.