Fig 3.

Cancer clonal evolution under therapy. a) Sequential, nonadaptive therapy. Conventional sequential therapy of two treatments selects for a clone resistant to treatment one (red) upon tumour relapse and subsequently a clone resistant to treatment two (green). b) Single drug adaptive therapy. Adaptive therapy maintains a stable tumour volume by introducing treatment holidays. Drug-sensitive clones (blue) suppress the growth of less-fit resistant clones (red). However, resistance still eventually occurs. c) Two drug sequential adaptive therapy. One proposed adaptive multidrug strategy is to alternately switch between drugs during each on–off cycle of tumour burden. d) Two drug concomitant adaptive therapy. An alternative multidrug adaptive strategy is to administer both drugs simultaneously during each on-off cycle, leading to a doubly resistant clone (yellow). Adapted with permission from West J, You L, Zhang J et al. Towards multidrug adaptive therapy. Cancer Res 2020;80:1578–89.