Figure 1: Schematic of cancer clonal evolution under therapy.

A) Conventional sequential therapy of two treatments selects for a clone resistant to treatment one (red) upon tumor relapse and subsequently a clone resistant to treatment two (green). B) Adaptive therapy maintains a stable tumor volume by introducing treatment holidays. Drug sensitive clones (blue) suppress the growth of less fit resistant clones (red). However, resistance still eventually occurs. C) One proposed adaptive multi-drug strategy is to alternately switch between drugs during each on-off cycle of tumor burden. D) An alternative multi-drug adaptive strategy is to administer both drugs simultaneously during each on-off cycle, leading to a doubly-resistant resistant clone (yellow).