The talk will discuss mathematical models of feedback regulation in tissues, and suggest that feedback networks that are operational in healthy tissue continue to function to a certain extent in tumors. It will then be shown how the presence of feedback regulatory networks in tumors can affect the response to chemotherapies. Specifically, this will be done in the context of bladder cancer treatment with chemotherapies. The mathematical models suggest that feedback networks can result in sustained enrichment of cancer stem cells within the tumor, which can correlate with a progressive loss of treatment response to chemotherapy, providing a non-genetic form of drug resistance. The mathematical results are related to in vivo experimental data from patient-derived bladder cancer xenografts.