Abstract
ABSTRACTChemovirotherapy is a combination therapy with chemotherapy and oncolytic viruses. It is gaining more interest and attracting more attention in the clinical setting due to its effective therapy and potential synergistic interactions against cancer. In this paper, we develop and analyse a mathematical model in the form of parabolic non-linear partial differential equations to investigate the spatiotemporal dynamics of tumour cells under chemovirotherapy treatment. The proposed model consists of uninfected and infected tumour cells, a free virus, and a chemotherapeutic drug. The analysis of the model is carried out for both the temporal and spatiotemporal cases. Travelling wave solutions to the spatiotemporal model are used to determine the minimum wave speed of tumour invasion. A sensitivity analysis is performed on the model parameters to establish the key parameters that promote cancer remission during chemovirotherapy treatment. Model analysis of the temporal model suggests that virus burst size and virus infection rate determine the success of the virotherapy treatment, whereas travelling wave solutions to the spatiotemporal model show that tumour diffusivity and growth rate are critical during chemovirotherapy. Simulation results reveal that chemovirotherapy is more effective and a good alternative to either chemotherapy or virotherapy, which is in agreement with the recent experimental studies.
Highlights
Current cancer treatments involve combination therapies such as radioimmunotherapy [29, 58], radiovirotherapy [15, 59], and immunotherapy combined with targeted therapies [23, 41, 63], to name but a few
We extend the growing literature on tumour virotherapy models by presenting a mathematical model of chemovirotherapy which builds upon those presented by Tian [57] and Malinzi et al [36]
To predict tumour cell densities at different time periods without the consideration of space, we first analyse and simulate the model without spatial dynamics which we present
Summary
Current cancer treatments involve combination therapies such as radioimmunotherapy [29, 58], radiovirotherapy [15, 59], and immunotherapy combined with targeted therapies [23, 41, 63], to name but a few. The study by Alonso et al [3] showed that the combination of an oncolytic adenovirus (ICOVIR-5), with either everolimus (RAD001) or temozolomide (TMZ) resulted in an enhanced increase in the anti-glioma effect in vitro and in vivo glioma xenograft model They concluded that the animals’ median survival rate has increased by 20–40% and that they remained disease free beyond 90 days after treatment. A recent experimental study by Gomez-Gutierrez et al [23] showed that the chemotherapeutic drug (TMZ) enhances virotherapy in three lung cancer cell lines, concluding that combined therapy of the oncolytic adenovirus (adeAdhz60) and TMZ has a synergistic killing effect in vitro.
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