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Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis

Enhancement of chemotherapy using oncolytic virotherapy: mathematical and optimal control analysis
Authors: Malinzi, Joseph; Ouifki, Rachid; Eladdadi, Amina; Torres, Delfim F.M.; White, K.A. Jane;

Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis

Abstract

Oncolytic virotherapy (OV) has been emerging as a promising novel cancer treatment that may be further combined with the existing therapeutic modalities to enhance their effects. To investigate how OV could enhance chemotherapy, we propose an ODE based model describing the interactions between tumour cells, the immune response, and a treatment combination with chemotherapy and oncolytic viruses. Stability analysis of the model with constant chemotherapy treatment rates shows that without any form of treatment, a tumour would grow to its maximum size. It also demonstrates that chemotherapy alone is capable of clearing tumour cells provided that the drug efficacy is greater than the intrinsic tumour growth rate. Furthermore, OV alone may not be able to clear tumour cells from body tissue but would rather enhance chemotherapy if viruses with high viral potency are used. To assess the combined effect of OV and chemotherapy we use the forward sensitivity index to perform a sensitivity analysis, with respect to chemotherapy key parameters, of the virus basic reproductive number and the tumour endemic equilibrium. The results from this sensitivity analysis indicate the existence of a critical dose of chemotherapy above which no further significant reduction in the tumour population can be observed. Numerical simulations show that a successful combinational therapy of the chemotherapeutic drugs and viruses depends mostly on the virus burst size, infection rate, and the amount of drugs supplied. Optimal control analysis was performed, by means of Pontryagin's principle, to further refine predictions of the model with constant treatment rates by accounting for the treatment costs and sides effects.

This is a preprint of a paper whose final and definite form is with 'Mathematical Biosciences and Engineering', ISSN 1551-0018 (print), ISSN 1547-1063 (online), available at [http://www.aimsciences.org/journal/1551-0018]. Submitted 27-March-2018; revised 04-July-2018; accepted for publication 10-July-2018

Countries
Portugal, South Africa
Keywords

Cells, Growth, Chemovirotherapy, Optimality conditions for problems involving ordinary differential equations, Models, Biological, Medical applications (general), Neoplasms, Cell Behavior (q-bio.CB), QA1-939, FOS: Mathematics, Animals, Humans, Computer Simulation, Oncolytic virotherapy, oncolytic virotherapy, Mathematics - Optimization and Control, optimal drug and virus combination, Oncolytic Virotherapy, chemovirotherapy, Mathematical Concepts, Combined Modality Therapy, 49K15, 92B05, Dynamics, Optimization and Control (math.OC), FOS: Biological sciences, Viruses, Optimal drug and virus combination, Quantitative Biology - Cell Behavior, Immunotherapy, Cancer chemotherapy, TP248.13-248.65, Mathematics, Biotechnology

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
57
Top 1%
Top 10%
Top 10%
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gold