Checkley, Stephen
MacCallum, Linda
Yates, James
Jasper, Paul
Luo, Haobin
Tolsma, John
Bendtsen, Claus
Article History
Received: 14 April 2015
Accepted: 30 July 2015
First Online: 27 August 2015
Change Date: 9 February 2016
Change Type: Update
Change Details: A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has been fixed in the paper.
Change Date: 9 February 2016
Change Type: Erratum
Change Details: Understanding the therapeutic effect of drug dose and scheduling is critical to inform the design and implementation of clinical trials. The increasing complexity of both mono, and particularly combination therapies presents a substantial challenge in the clinical stages of drug development for oncology. Using a systems pharmacology approach, we have extended an existing PK-PD model of tumor growth with a mechanistic model of the cell cycle, enabling simulation of mono and combination treatment with the ATR inhibitor AZD6738 and ionizing radiation. Using AZD6738, we have developed multi-parametric cell based assays measuring DNA damage and cell cycle transition, providing quantitative data suitable for model calibration. Our <i>in vitro</i> calibrated cell cycle model is predictive of tumor growth observed in <i>in vivo</i> mouse xenograft studies. The model is being used for phase I clinical trial designs for AZD6738, with the aim of improving patient care through quantitative dose and scheduling prediction.
Competing interests
: The authors declare no competing financial interests.