Goldie-Coldman hypothesis

Gol·die-Cold·man hypothesis

(gōl'dē cōld'măn), 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.
A posit that the emergence of chemotherapy-resistant subclones of malignant cells arise at a rate related to the genetic instability. Resistance is a process of selection. Rate of development of drug resistance is independent of number of cells, but the absolute number of resistant cells is still greater