Modelling acquired drug resistance in tumours: Effects of mutations and cell competition

Acquired drug resistance is a process during which the cancer cells develop immunity to the chemotherapeutic drug over the course of treatment and poses a major obstacle in effective chemotherapy protocol planning. In 2009 Morno and Gaffney published an article in Journal of Theoretical Biology entitled  "Modelling chemotherapy resistance in palliation and failed cure". In the article a simple model of tumour with Gompertzian dynamics with mutations was considered. Based on numerical simulations they concluded that reduced-dose protocols may lead to improved
survival times and, interestingly, that starting treatment too early maydecrease survival time. During the first part of our talk we will present results of this work. Second part of our talk will be devoted to a modified model which takes into acount competition between resistant and sensitive tumour cells. The emergence of drug resistance is usually attributed to the high mutation and proliferation rates exhibited by cancer cells. Our preliminary results, however, suggest that this process is heavily influenced by cell competition. Finally, we will show how the way chemotherapy response is modelled influences the results. In particular, we will examine the differences between a linear response and one based on Norton-Simon hypothesis.