Dr Kevin Owen Hicks
Kevin obtained his veterinary training and BVSc from the Massey University and PhD in Pharmacology from The University of Auckland.
- Anticancer drug development
- Tumour hypoxia
- Drug transport in tumours
- Pharmacokinetic modelling
- Pharmacodynamic modelling
Research | Current
- The use of 3-dimensional tissue culture techniques to investigate anticancer drug transport and activity.
- Spatially resolved pharmacokinetic/pharmacodynamic modelling of anticancer drug transport and cytotoxicity.
- The design, synthesis, and evaluation of novel 1,2,4-benzotriazine dioxides as hypoxia-selective cytotoxins bioreductive drugs.
Kevin's research involves the use of multicellular layers (MCL) to investigate the extravascular transport of anticancer drugs. Multicellular layers are a model for the tumour extravascular compartment similar to multicellular spheroids but their planar geometry diffusion studies to be performed in diffusion chambers to assess drug transport.
Results of MCL studies require interpretation by modelling drug transport in tumours constrained by tumour geometry and blood/plasma drug pharmacokinetics. In collaboration with Dr Timothy Secomb at The University of Arizona and Dr Mark Dewhirst at The tumor Microcirculation Laboratory, Duke University we have developed a spatially resolved 3-dimensional PK/PD model for the extravascular transport of hypoxic cytotoxins. This program is available for download on Kevin's homepage.
These techniques can be used to assist in drug design programs in order to introduce PK/PD and, in particular, extravascular transport early in the drug design process.
Current Post-Graduate Students
Mohammed Abuwarwar, The relationship between cell killing by SN30000/radiation combinations and growth delay in multicellular tumour spheroids, MSc
Cho Rong Hong, Bystander effects of hypoxia activted prodrugs in multicellular spheroids and tumours
Xinjian Mao, Drug and radiation interactions with hypoxia activted prodrugs in three dimensional cell cultures
Hong Nam Shin, The pH and Pka dependence of cellular metabolism and cygotoxicity of dual hypoxia and pH acid BTO analogues, MSc
Selected publications and creative works (Research Outputs)
- Gu, Y., Chang, T. T.-A., Wang, J., Jaiswal, J. K., Edwards, D., Downes, N. J., ... Hickey, A. J. (2017). Reductive metabolism influences the toxicity and pharmacokinetics of the hypoxia-targeted benzotriazine di-oxide anticancer agent SN30000 in mice. Frontiers in Pharmacology, 8, 1-16. 10.3389/fphar.2017.00531
Other University of Auckland co-authors: Tony Hickey, Yongchuan Gu, Jagdish Jaiswal, Frederik Pruijn, Michael Hay, William Wilson, Courtney Lynch
- Hicks, K. O. (2015). Modelling hypoxia activated prodrugs in vitro and in silico (Invited Lecture). Auckland Bioengineering Institute. Related URL.
- Hicks, K. O. (2015). Intratumour pharmacokinetics in cancer drug discovery and development. Paper presented at New Zealand Society for Oncology Conference, Christchurch, New Zealand. 2 November - 3 November 2015. Related URL.
- Foehrenbacher, A., Secomb, T. W., Wilson, W. R., & Hicks, K. O. (2013). Design of optimized hypoxia-activated prodrugs using pharmacokinetic/pharmacodynamic modeling. Frontiers in Oncology, 310.3389/fonc.2013.00314
Other University of Auckland co-authors: William Wilson
- Foehrenbacher, A., Patel, K., Abbattista, M. R., Guise, C. P., Secomb, T. W., Wilson, W. R., & Hicks, K. O. (2013). The role of bystander effects in the antitumor activity of the hypoxia-activated prodrug PR-104. Frontiers in Oncology, 3 (263).10.3389/fonc.2013.00263
Other University of Auckland co-authors: William Wilson, Christopher Guise, Maria Abbattista
- Hicks, K. O. (2013). Introducing Drug Transport Early in the Design of Hypoxia Selective Anticancer Agents Using a Mathematical Modelling Approach. In D'Onofrio A, P. Cerrai, A. Gandolfi (Eds.) New Challenges for Cancer Systems Biomedicine (pp. 337-353). Italia: Springer. 10.1007/978-88-470-2571-4
- Hicks, K. O., Siim, B. G., Jaiswal, J. K., Pruijn, F. B., Fraser, A. M., Patel, R., ... Brown, J. M. (2010). Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors. Clin Cancer Res, 16 (20), 4946-4957. 10.1158/1078-0432.CCR-10-1439
Other University of Auckland co-authors: Michael Hay, Jagdish Jaiswal, Bill Denny, Frederik Pruijn, William Wilson