Tumor treatment with chemo-virotherapy and MEK inhibitor: A mathematical model of Caputo fractional differential operator

Abstract

Mitogen-activated protein kinase (MEK) inhibitors and oncolytic virotherapy are identified as promising cancer therapies that can enhance the efficacy of other cancer treatments. A few studies demonstrate that cancer cells proliferate when exposed to virotherapy with MEK inhibitors in an integer order model or without them in a fractional order model. None of them are intended to investigate tumor cell growth under the combined treatment strategy of chemo-virotherapy with a MEK inhibitor in a fractional order model. In this paper, a mathematical model based on fractional order ordinary differential equations (ODEs) is developed for the mutual interactions among tumor cells, as well as a therapeutic combination of chemotherapy, oncolytic viruses and the functional consequence of MEK inhibitor, to investigate how virotherapy could enhance chemotherapy under the action of MEK inhibitor. The numerical results show that virus burst size and MEK inhibitors have a noticeable impact on regulating the trend of tumor cell proliferation. While virotherapy responses to tumor cell proliferation are undoubtedly quicker than chemotherapeutic treatment responses, MEK intensity clearly affects the success of the treatment regimen. The results of this study can contribute to the development of a therapeutic strategy that combines MEK inhibitor functional monitoring with tumor cell growth control.