hypothesis that a tumor is composed of populations of faster-growing cells, which are sensitive to therapy, and slower-growing, more resistant cells. Given that only therapy that completely eradicates all tumor cells will be curative, this is most likely to occur with sequential, non-cross-resistant regimens. The initial regimen must be effective enough to result in a low residual tumor burden and is followed by one or more non-cross-resistant treatments to eradicate the remainder of the cancer.