Ali, Reza, Evans, N. D., Campbell, Lee, Errington, Rachel J., Godfrey, Keith R., Smith, Paul J. (Paul James), 1953- and Chappell, M. J. (Michael J.) (2007) Modelling the control of cell proliferation by an anti-cancer agent. Measurement & Control, Vol.40 (No.1). pp. 12-15. ISSN 0020-2940

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Abstract

A mathematical model has been developed which describes human cell growth in the presence of topotecan (TPT), an anti-cancer agent. Previously, a model was developed for the pharmacokinetics (PK) of TPT, this provided a description of the activity of TPT and the subsequent delivery of the active form to the nuclear DNA target. This model is described briefly in this paper. The development of a new pharmacodynamic (PD) model for cell growth, based on a well-known cell cycle model is then discussed. The linking of the PK model to the PD model is considered with respect to the modulation of cell growth. Our PK-PD model has good agreement with in vitro experimental data. In a clinical context, it is intended that the model will be used for discovering routes for drug resistance and eventually as a tool for improving drug treatments for patients.

Item Type:	Submitted Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Science > Engineering
Library of Congress Subject Headings (LCSH):	Cells -- Growth -- Mathematical models, Antineoplastic agents -- Mathematical models, Drugs -- Physiological effect -- Mathematical models
Journal or Publication Title:	Measurement & Control
Publisher:	Sage Publications Ltd.
ISSN:	0020-2940
Date:	February 2007
Volume:	Vol.40
Number:	No.1
Number of Pages:	4
Page Range:	pp. 12-15
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Research Councils UK (RCUK)
Grant number:	88/E19305 (BBSRC)
References:	[1] Bailly, C., “Topoisomerase I poisons and suppressors as anticancer drugs” Current Medicinal Chemistry, 7, pp. 39-58, 2000. [2] Wang, J.C., “DNA topoisomerases”, Annual Review of Biochemistry, 65, pp. 635-692, 1996. [3] Evans, N.D., Errington, R.J., Chapman, M.J., Smith, P.J., Chappell, M.J. and Godfrey, K.R., “Compartmental modelling of the uptake kinetics of the anti-cancer agent topotecan in human breast cancer cells” International Journal of Adaptive Control & Signal Processing, 19(5), pp. 395-417, 2005. [4] Tyson, J.J. and Novak, B., “Regulation of the eukaryotic cell cycle: molecular antagonism, hysteresis and irreversible transitions”, Journal of Theoretical Biology, 210(2), pp. 249-263, 2001. [5] Errington, R.J., Ameer-beg, S.M., Vojnovic, B., Patterson, L.H., Zloh, M. and Smith, P.J., “Advanced microscopy solutions for monitoring the kinetics and dynamics of drug-DNA targeting in living cells”, Advanced Drug Delivery Reviews, 57(1), pp. 153-167, 2005. [6] Chourpa, I., Millot, J.M., Sockalingum, C.D., Riou, J.F. and Manfait, M. “Kinetics of lactone hydrolysis in antitumor drugs of camptothecin series as studied by fluorescence spectroscopy”, Biochimica et Biophysica Acta, 1379(3), pp. 353-366, 1998. [7] MCPA Software Ltd, FACSIMILE for Windows (Version 4.0) User Guide, www.mcpa-software.com, 2004. [8] Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K. and Watson, J.D., Molecular Biology of the Cell (3rd Edition), New York: Garland Publishing, 1994. [9] Thomas, N. and Goodyear, I. D., “Stealth sensors: real-time monitoring of the cell cycle”, Targets, 2, pp. 26-33, 2003. [10] Feeney, G.P., Errington, R.J., Wiltshire, M., Marquez, N., Chappell, S.C. and Smith, P. J., “Tracking the cell cycle origins for escape from topotecan action by breast cancer cells”, British Journal of Cancer, 88(8), pp. 1310-1317, 2003. [11] Pérez-Urizar, J., Granados-Soto, V., Flores-Murrieta, F.J., and Castañeda-Hernández, G., “Pharmacokinetic-pharmacodynamic modelling: why?” Archives of Medical Research, 31(6), pp. 539-545, 2000. [12] Alarcón, T., Byrne, H.M. and Maini, P.K., “A mathematical model of the effects of hypoxia on the cell-cycle of normal and cancer cells”, Journal of Theoretical Biology, 229(3), pp. 395-411, 2004.
URI:	http://wrap.warwick.ac.uk/id/eprint/32123

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