Treatment of evolving cancers will require dynamic decision support.

ABSTRACT

Cancer research has traditionally focused on developing new agents, but an underexplored question is that of the dose and frequency of existing drugs. Based on the modus operandi established in the early days of chemotherapies, most drugs are administered according to predetermined schedules that seek to deliver the maximum tolerated dose and are only adjusted for toxicity. However, we believe that the complex, evolving nature of cancer requires a more dynamic and personalized approach. Chronicling the milestones of the field, we show that the impact of schedule choice crucially depends on processes driving treatment response and failure. As such, cancer heterogeneity and evolution dictate that a one-size-fits-all solution is unlikely-instead, each patient should be mapped to the strategy that best matches their current disease characteristics and treatment objectives (i.e. their 'tumorscape'). To achieve this level of personalization, we need mathematical modeling. In this perspective, we propose a five-step 'Adaptive Dosing Adjusted for Personalized Tumorscapes (ADAPT)' paradigm to integrate data and understanding across scales and derive dynamic and personalized schedules. We conclude with promising examples of model-guided schedule personalization and a call to action to address key outstanding challenges surrounding data collection, model development, and integration.