Optimal Control Model of Tumor Treatment with Oncolytic Virus and MEK Inhibitor

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2017 Jan 19

PMID 28097139

Citations 1

Authors

Yongmei Su

Chen Jia

Ying Chen

Affiliations

Soon will be listed here.

Abstract

Tumors are a serious threat to human health. The oncolytic virus is a kind of tumor killer virus which can infect and lyse cancer cells and spread through the tumor, while leaving normal cells largely unharmed. Mathematical models can help us to understand the tumor-virus dynamics and find better treatment strategies. This paper gives a new mathematical model of tumor therapy with oncolytic virus and MEK inhibitor. Stable analysis was given. Because mitogen-activated protein kinase (MEK) can not only lead to greater oncolytic virus infection into cancer cells, but also limit the replication of the virus, in order to provide the best dosage of MEK inhibitors and balance the positive and negative effect of the inhibitors, we put forward an optimal control problem of the inhibitor. The optimal strategies are given by theory and simulation.

Citing Articles

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Gluzman M, Scott J, Vladimirsky A Proc Biol Sci. 2020; 287(1925):20192454.

PMID: 32315588 PMC: 7211445. DOI: 10.1098/rspb.2019.2454.

References

Bagheri N, Shiina M, Lauffenburger D, Korn W . A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition. PLoS Comput Biol. 2011; 7(2):e1001085. PMC: 3040662. DOI: 10.1371/journal.pcbi.1001085. View

Ganly I, Kirn D, Eckhardt G, Rodriguez G, Soutar D, Otto R . A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res. 2000; 6(3):798-806. View

Anders M, Christian C, McMahon M, McCormick F, Korn W . Inhibition of the Raf/MEK/ERK pathway up-regulates expression of the coxsackievirus and adenovirus receptor in cancer cells. Cancer Res. 2003; 63(9):2088-95. View

Patel M, Kratzke R . Oncolytic virus therapy for cancer: the first wave of translational clinical trials. Transl Res. 2013; 161(4):355-64. DOI: 10.1016/j.trsl.2012.12.010. View

Wodarz D . Viruses as antitumor weapons: defining conditions for tumor remission. Cancer Res. 2001; 61(8):3501-7. View

Tian J . The replicability of oncolytic virus: defining conditions in tumor virotherapy. Math Biosci Eng. 2011; 8(3):841-60. DOI: 10.3934/mbe.2011.8.841. View

Komarova N, Wodarz D . ODE models for oncolytic virus dynamics. J Theor Biol. 2010; 263(4):530-43. PMC: 2839021. DOI: 10.1016/j.jtbi.2010.01.009. View

Russell S, Peng K, Bell J . Oncolytic virotherapy. Nat Biotechnol. 2012; 30(7):658-70. PMC: 3888062. DOI: 10.1038/nbt.2287. View

S Novozhilov A, Berezovskaya F, Koonin E, P Karev G . Mathematical modeling of tumor therapy with oncolytic viruses: regimes with complete tumor elimination within the framework of deterministic models. Biol Direct. 2006; 1:6. PMC: 1403749. DOI: 10.1186/1745-6150-1-6. View

10.

Donnelly O, Errington-Mais F, Prestwich R, Harrington K, Pandha H, Vile R . Recent clinical experience with oncolytic viruses. Curr Pharm Biotechnol. 2011; 13(9):1834-41. DOI: 10.2174/138920112800958904. View

11.

Rauen K, Sudilovsky D, Le J, Chew K, Hann B, Weinberg V . Expression of the coxsackie adenovirus receptor in normal prostate and in primary and metastatic prostate carcinoma: potential relevance to gene therapy. Cancer Res. 2002; 62(13):3812-8. View

12.

Lacher M, Tiirikainen M, Saunier E, Christian C, Anders M, Oft M . Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition. Cancer Res. 2006; 66(3):1648-57. DOI: 10.1158/0008-5472.CAN-05-2328. View

13.

Rodriguez R, Schuur E, Lim H, Henderson G, Simons J, Henderson D . Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res. 1997; 57(13):2559-63. View

14.

Bajzer Z, Carr T, Josic K, Russell S, Dingli D . Modeling of cancer virotherapy with recombinant measles viruses. J Theor Biol. 2008; 252(1):109-22. DOI: 10.1016/j.jtbi.2008.01.016. View

15.

Cherubini G, Petouchoff T, Grossi M, Piersanti S, Cundari E, Saggio I . E1B55K-deleted adenovirus (ONYX-015) overrides G1/S and G2/M checkpoints and causes mitotic catastrophe and endoreduplication in p53-proficient normal cells. Cell Cycle. 2006; 5(19):2244-52. DOI: 10.4161/cc.5.19.3263. View

16.

Aghi M, Martuza R . Oncolytic viral therapies - the clinical experience. Oncogene. 2005; 24(52):7802-16. DOI: 10.1038/sj.onc.1209037. View

17.

Zurakowski R, Wodarz D . Model-driven approaches for in vitro combination therapy using ONYX-015 replicating oncolytic adenovirus. J Theor Biol. 2006; 245(1):1-8. PMC: 2712658. DOI: 10.1016/j.jtbi.2006.09.029. View

18.

Kelly E, Russell S . History of oncolytic viruses: genesis to genetic engineering. Mol Ther. 2007; 15(4):651-9. DOI: 10.1038/sj.mt.6300108. View

19.

Si W, Zhang W . Control exponential growth of tumor cells with slow spread of oncolytic virus. J Theor Biol. 2014; 367:111-129. DOI: 10.1016/j.jtbi.2014.11.015. View

20.

Miest T, Cattaneo R . New viruses for cancer therapy: meeting clinical needs. Nat Rev Microbiol. 2013; 12(1):23-34. PMC: 4002503. DOI: 10.1038/nrmicro3140. View