Fig. 2

Top panel. Current chemotherapy regimens initially cause a major reduction of the tumor size, which mostly kills chemo-sensitive cells. This creates a powerful selective pressure that will inevitably benefit clones (shown in dark gray) that have intrinsic resistance to the treatment. Thus, chemo-resistant clones, now unhindered by competition from chemo-sensitive clones, can repopulate the landscape and eventually emigrate to other tissues. Bottom panel. Proposed adaptive cancer therapy, in which the tumor is partially debulked with a mild chemotherapy regimen but where a portion of the chemo-sensitive population is allowed to survive and oppose the growth of chemo-resistant clones (dark gray cells). Thus, this type of treatment would cause the tumor size to follow a sinusoid growth curve with periods of growth and shrinkage. This approach should control tumor burden but without the goal of complete eradication of the disease