Optimal drug treatment for reducing long-term drug resistance

The maximum-tolerated dose principle, the highest possible drug dose in the shortest possible time period, has been the standard care for cancer treatment. Although it is appealing in a homogeneous tumor setting, tumor heterogeneity and adaptation play a significant role in driving treatment failure. They are still major obstacles in cancer treatments despite great advances in modeling and cancer therapy using optimal control theory. To address this, we first generalize two population models and examine the long-term effects of differential selective treatment strategies. Second, we take into account different drug-imposed selective pressure into designing optimal treatment strategies. Numerical examples demonstrate that the proposed treatment strategy decreases long-term tumor burden by decreasing the rate of tumor adaptation.