A mathematical model to study the effect of drug kinetics on the drug-induced resistance in tumor growth dynamics

Abstract

Abstract Drug resistance is recognized as being the major obstacle to be overcome during the systemic chemotherapy of cancer. Tremendous amounts of molecular mechanisms results in resistance in the cell as they develop. Resistance always arises after drug application. The rate at which resistance occurs under mutation induced by drug is affected by drug kinetics. Yet, it isn’t clear how drug kinetic factors affect the evolution of resistance. Here, we developed a mathematical model to describe the growth of the resistant subpopulation along with the effect of different drugs administrated. In the model, we took into account how two critical kinetic factors for each drug, drug eradication rate and drug-induced resistance mutation rate, determine the treatment result. We calculated the drug dosage threshold for the maximum resistance and found that it only related to eradication rate. The combined analysis of the model and clinical data might give useful information on the treatment strategies and be potentially useful for designing specifically tailored cancer therapies with individual drugs.