Modelling of tumour growth and cytotoxic effect of docetaxel in xenografts.
One of the major sources of information on physiological and pathophysiological effects in pre-clinical oncology studies is the xenografted tumour animal model. However, measurement of tumour volume over time potentially masks a range of biological changes that the xenograft is undergoing. In this paper a mechanistic model of tumour growth in xenografts is presented that can be used to investigate the mode of drug action with respect to phenotypic changes. The model encapsulates key histological biomarkers and spatial constraints. The unknown model parameters are first shown to be uniquely identifiable from the proposed experimental studies, and then estimated from the resulting data using the anti-cancer agent docetaxel.
School of Engineering, University of Warwick, Coventry CV4 7AL, UK. Electronic address: Neil.Evans@warwick.ac.uk.
Neil D
ND
Evans
Wright Dose Ltd, Charter House, 2 Woodlands Road, Altrincham, Cheshire WA14 1HF, UK.
Richard J
RJ
Dimelow
Modelling and Simulation, DMPK, AstraZeneca Ltd, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
James W T
JW
Yates
D000465:Algorithms; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D012984:Software; D043823:Taxoids / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel
Biomedical systems; Cytotoxic agents; Parameter estimation; Structural identifiability; Tumour growth models; Xenograft tumour models