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)
- Hong, C. R., Dickson, B. D., Jaiswal, J. K., Pruijn, F. B., Hunter, F. W., Hay, M. P., ... Wilson, W. R. (2018). Cellular pharmacology of evofosfamide (TH-302): A critical re-evaluation of its bystander effects. Biochemical Pharmacology, 156, 265-280. 10.1016/j.bcp.2018.08.027
Other University of Auckland co-authors: Benjamin Dickson, Michael Hay, Jagdish Jaiswal, Frederik Pruijn, Francis Hunter
- Hong, C. R., Bogle, G., Wang, J., Patel, K., Pruijn, F. B., Wilson, W. R., & Hicks, K. O. (2018). Bystander Effects of Hypoxia-Activated Prodrugs: Agent-Based Modeling Using Three Dimensional Cell Cultures. FRONTIERS IN PHARMACOLOGY, 910.3389/fphar.2018.01013
Other University of Auckland co-authors: Gib Bogle, Frederik Pruijn
- Jamieson, S. M. F., Tsai, P., Kondratyev, M. K., Budhani, P., Liu, A., Senzer, N. N., ... Kee, D. (2018). Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma. JCI INSIGHT, 3 (16)10.1172/jci.insight.122204
Other University of Auckland co-authors: Francis Hunter, Stephen Jamieson, Peter Tsai, Avik Shome, Nicholas Knowlton, Tet Woo Lee, Stefan Bohlander, Purvi Kakadiya
- Bonnet, M., Hong, C. R., Wong, W. W., Liew, L. P., Shome, A., Wang, J., ... Anderson, R. F. (2018). Next-generation hypoxic cell radiosensitizers: Nitroimidazole alkylsulfonamides. Journal of Medicinal Chemistry, 61 (3), 1241-1254. 10.1021/acs.jmedchem.7b01678
Other University of Auckland co-authors: Michael Hay, Lydia Liew, Way Wong, Bob Anderson, Stephen Jamieson, Frederik Pruijn, Yongchuan Gu, Ralph Stevenson, Avik Shome
- 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
- Mao, X., Bogle, G., McManaway, S., Wilson, W., & Hicks, K. (2017). Agent-based models for prediction of tumor spheroid response to radiation and the hypoxia-activated prodrug SN30000. Paper presented at AACR (American Association for Cancer Research) Annual Meeting 2017, Washington, DC. 1 April - 5 April 2017. Proceedings of the American Association for Cancer Research.
Other University of Auckland co-authors: Gib Bogle
- Hay, M. P., Hicks, K. O., & Wilson, W. R. (2017). Discovery of the hypoxia-activated prodrug SN30000. In S. Chackalamannil, D. Rotella, S. Ward (Eds.) Comprehensive medicinal chemistry III. Volume 8, Case histories in recent drug discovery (pp. 58-94). Oxford, UK: Elsevier. 10.1016/B978-0-12-409547-2.12450-3
Other University of Auckland co-authors: Michael Hay, William Wilson
- Campbell, E. J., Vissers, M. C. M., Wohlrab, C., Hicks, K. O., Strother, R. M., Bozonet, S. M., ... Dachs, G. U. (2016). Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice. Free Radical Biology and Medicine, 99, 451-462. 10.1016/j.freeradbiomed.2016.08.027