Monitoring and improving the uptake of anticancer drugs in tumours
For anticancer drugs to be effective they must reach all of the cells in a tumour but many parts of the tumour receive little or no drug and therefore we aim to establish how drugs can be modified to enable them to diffuse throughout a tumour and are using a variety of cutting edge visualization technologies to track the uptake of our new compounds in tumours and tumour models.
Chemotherapy is one of the primary modalities of cancer treatment, but in only a small proportion of cases is it alone able to completely and permanently eradicate the disease. For an anticancer drug to be effective it must reach all of the viable cells in a tumour (macroscopic uptake) and then be taken up by those cells (cellular uptake) in sufficient concentrations to inhibit its molecular target and initiate cell death. However, macroscopic uptake in tumours can be highly non-uniform because of poor vascularisation and limited diffusion from the blood vessels. For instance, it has been shown using fluorescence microscopy that the anticancer drug doxorubicin (Adriamycin) only diffuses 40-100 microns from the blood vessels and therefore only reaches a fraction of the viable cells that make up a solid tumour (Figure 1). Of particular concern are the hypoxic regions of solid tumours which are usually greater than 100 microns from the blood vessels and contain the cells with the most aggressive and drug resistant phenotypes. The inability of anticancer drugs to reach all cells in concentrations sufficient to exert an effect is believed to be a major contributor to the frequent failure of chemotherapy to completely eradicate tumours.
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.
Want to find out more?
The opportunity ID for this research opportunity is: 557