About Professor Trevor Hambley
Professor Hambley is leading the development of new methods for monitoring and modifying the distribution of anticancer drugs in solid tumours and new methods for identifying and targeting tumours.
Professor Hambley’s primary research interests lie in the area of medicinal inorganic chemistry; the use of metals and metal complexes, such as platinum complexes, to detect and treat disease, particularly cancer. Platinum drugs are the mainstay of many anticancer treatments, but his group has recently shown that they undergo limited diffusion in solid tumour models. It is now believed that similarly limited diffusion applies to most if not all classes of anticancer drugs and is a major cause of treatment failure. Worse still, the cells in the tumour that are subjected to a sub-lethal dose of the anticancer agent are likely to develop resistance to the treatment. Also, those cells that receive the lowest dose of drugs are those that also receive low concentrations of oxygen and other nutrients and as a consequence have frequently developed features that contribute to the tumour being more aggressive and difficult to treat. Thus, the seemingly simple notion of the distribution of an anticancer drug throughout a solid tumour has emerged as one of the major factors impeding more effective cancer treatment. Professor Hambley and his group have as their goal the development of tools for monitoring the distribution and activation of drugs and prodrugs through tumours and tumour models and the development of the drug design principles that will allow distribution throughout the tumour.
Professor Hambley has been responsible for major developments in medicinal inorganic chemistry, particularly in the area of Pt anticancer drugs. Prof. Hambley and his group have been the first to develop synchrotron radiation based methods for the in situ determination of oxidation states of platinum in biological environments and for reliably determining platinum distributions in these environments. He and his group developed cobalt complexes as delivery agents for anticancer drugs, showing that such complexes are more effective than the free inhibitor, and developed fluorophore tagged cobalt complexes that show when and where the inhibitors are released in biological systems.
Prof. Hambley has published 3 books, 5 book chapters, 14 reviews, and more than 430 refereed journal papers, including eight recent reviews on metal based therapeutics and an invited perspective in Science on the same subject. Prof. Hambley has been invited to present the results of his work as a keynote or plenary speaker at more than 20 major international meetings since 1999. Prof. Hambley has had continuous ARC funding since 1992 (totalling in excess of $6 million). Prof. Hambley has supervised more than 20 PhD students and 40 Honours students. In recognition of the quality of his research supervision, he received the “Supervisor of the Year” award at the University of Sydney in 1997 and an Excellence in Teaching Award for Postgraduate Supervision in 1998. Prof. Hambley has extensive experience working with pharmaceutical industry, as a consultant and as a collaborative researcher and as an expert witness. Professor Hambley is a member of the Council of the Society of Biological Inorganic Chemistry, the peak international body in this area, and was recently elected to the position of President of this body, a role he will assume on July 1, 2008.Note: Professor Hambley’s group and facilities encompasses the full range of techniques from drug design and synthetic chemistry, through characterization, in vitro biological studies and visualization. They make extensive use of confocal microscopy to study cells and tumour cell spheroids and use synchrotron techniques (XANES, SRIXE, and XAFS) to complement the information obtained using the visible spectroscopy.Scholarships are available to high quality students. Most local students in the laboratory are supported by an Australian or University Postgraduate Award and International students by other scholarships. Please contact me for further details.
- Alderden, RA, Mellor, HR, Modok, S, Hall, MD, Sutton, SR, Newville, MG, Callaghan, R and Hambley, TW. Elemental Tomography of Cancer Cell Spheroids Reveals Incomplete Uptake of both Platinum (II) and Platinum (IV) Complexes. J. Amer. Chem. Soc, 129, 13400-13401, 2007.
- Hall, MD, Yamamoto, N and Hambley, TW. Bioreductive Activation and Drug Chaperoning in Cobalt Pharmaceuticals. Dalton Trans., 3983-3990, 2007.
- Hall, MD, Mellor, HR, Callaghan, R and Hambley, TW. The Basis for Design and Development of Platinum(IV) Anticancer Complexes. J. Med. Chem., 50, 3403-3411, 2007.
- Hambley, TW. Developing New Metal-Based Therapeutics: Challenges and Opportunities. Dalton Trans., 4929-4937, 2007.
- Failes, TW, Cullinane, C, Diakos, CI, Yamamoto, N, Lyons, JG and Hambley, TW. A Co(III) Complex of the MMP Inhibitor Marimastat: A Potential Hypoxia Activated Prodrug. Chem. Eur J., 13, 2974-2982, 2007.
- Mellor, HR, Snelling, S, Hall, MD, Modok, S, Jaffar, M, Hambley, TW and Callaghan, R. The Influence of Tumour Microenvironmental Factors on the Efficacy of Cisplatin and Novel Platinum(IV) Complexes. Biochem. Pharmacol., 70, 1137-1146, 2005.
- Hall, MD, Dolman, R and Hambley, TW. Platinum(IV) Anticancer Complexes. Metal Complexes in Tumor Diagnosis and as Anticancer Agents. Volume 42 of “Metal Ions in Biological Systems” A. Sigel and H. Sigel, editors., M. Dekker, New York & Basel, Ch. 9, pp 297–322, 2004.
- Hall, MD, Martin, C, Ferguson, DJP, Phillips, RM, Hambley, TW and Callaghan, R. Comparative Efficacy of Novel Platinum(IV) Compounds with Established Chemotherapeutic Drugs in Solid Tumour Models. Biochemical Pharmacology, 67, 17-30, 2004.
- Hall, MD, Foran, GJ, Zhang, M, Beale, PJ and Hambley, TW. XANES Determination of the Platinum Oxidation State Distribution in Cancer Cells Treated with Platinum(IV) Anticancer Agents. J. Am. Chem. Soc., 125, 7524–7525, 2003.
- Hall, MD, Dillon, CT, Zhang, M, Beale, P, Cai, Z, Lai, B, Stampfl, APJ and Hambley, TW. The Cellular Distribution and Oxidation State of Platinum(II) and Platinum(IV) Antitumour Complexes in Cancer Cells. JBIC, 8, 726–732, 2003.