The effect of cellular differentiation on the development of permanent drug resistance (Q1064978)

Birth and death processes are applied to modeling of development of spontaneous drug resistance of tumor stem cells. It is supposed that new stem cells are produced at a rate b, while the existing stem cells differentiate (leave the system) at rate d. Resistance to drug is caused by a single mutation occuring at a rate \(\alpha\). Cell death is not considered. The authors carefully investigate the Kolmogorov equations of the process to find expected values and extinction probabilities yielded by the model. It is found that cell differentiation increases the rate of development of single drug resistance, although this is balanced by an increased likelihood that such resistant cells sooner leave the stem cell population. Situation changes if resistance to two drugs is considered; then the probability that doubly resistant cells persist, is proportional to the rate of cell differentiation. A discussion of the validity of assumptions used, is provided.