Spatio-temporal model of combining chemotherapy with senolytic treatment in lung cancer

Abstract

Senescent cells are cells that stop dividing but sustain viability. Cellular senescence is the hallmark of aging, but senescence also appears in cancer, triggered by cells stress, tumor suppression of gene activation, and oncogene activity. In lung cancer, senescent cancer cells secrete VEGF, which initiates a process of angiogenesis, enabling the cancer to grow and proliferate. Chemotherapy kills cancer cells, but some cancer cells become senescent. Hence, a senolytic drug, a drug that eliminates senescent cells, should significantly improve the efficacy of chemotherapy. In this paper, we developed a mathematical spatio-temporal model of combination chemotherapy with senolytic drug in treatment of lung cancer. Model’s simulations of tumor volume growth are shown to agree with mouse experiments in the case where cyclophosphamide is combined with the senolytic drug fisetin. It is then shown how the model can be used to assess the benefits of treatments with different combinations and different schedules of the two drugs in order to achieve optimal tumor volume reduction.