a mathematic model that predicts that tumor cells mutate to a resistant phenotype at a rate dependent on their intrinsic genetic instability. The probability that a cancer would contain drug-resistant clones depends on the mutation rate and the size of the tumor. According to this hypothesis, even the smallest detectable cancers would contain at least one drug-resistant clone; therefore, the best chance of cure would be to use all effective chemotherapy drugs; in practice, this has meant using two different non-cross-resistant chemotherapy regimens in alternating cycles.