Angiogenesis and chemotherapy resistance: optimizing chemotherapy scheduling using mathematical modeling

Chemotherapy remains a widely used cancer treatment. Acquired drug resistance may greatly reduce the efficacy of treatment and means to overcome it are a topic of active discussion among researchers. One of the proposed solutions is to change the therapeutic target to maintenance rather than complete eradication of cancer, i.e. to treat it as a chronic disease. Using mathematical modeling and optimal control techniques we would like to investigate the hypothesis that lower doses of chemotherapy may be beneficial for patients. We formulate a mathematical model of tumor growth under angiogenic signaling based on Hahnfeldt et al. model, which we adapt to heterogeneous tumors treated by combined anti-angiogenic agent and chemotherapy. Our analysis offers insights into the effects of metronomic therapy. We will discuss our recent results, where the chemotherapy-sensitive cells are killed by the drug according to the log-kill hypothesis and a modification of the model, where the Norton-Simon hypothesis is applied.