Enhancement of chemotherapy using oncolytic virotherapy: mathematical and optimal control analysis
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Publication:2000772
DOI10.3934/MBE.2018066zbMATH Open1416.92091arXiv1807.04329OpenAlexW2834875999WikidataQ59351273 ScholiaQ59351273MaRDI QIDQ2000772FDOQ2000772
Rachid Ouifki, K. A. Jane White, Delfim F. M. Torres, Joseph Malinzi, Amina Eladdadi
Publication date: 28 June 2019
Published in: Mathematical Biosciences and Engineering (Search for Journal in Brave)
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.
Full work available at URL: https://arxiv.org/abs/1807.04329
Medical applications (general) (92C50) Optimality conditions for problems involving ordinary differential equations (49K15)
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