Cutting-edge cancer research
We’re exploring a range of treatments, including overcoming drug resistance, and technologies to diagnose and combat various types of cancer, including those hardest to combat, such as breast and prostate cancers, and brain tumours.
New approach for brain tumour sufferers
Brain tumours are one of the most aggressive forms of cancer and one of the hardest to treat. Critically, resistance to chemotherapy is a major problem. Research led by GRIDD Professor Sally-Ann Poulsen, in collaboration with Italian researchers, may offer new hope to combat this disease by altering the environment that enables brain cancer cells to resist current chemotherapy drugs.
‘Cancer cells become drug resistant by expressing a protein that pumps chemotherapy drugs out of the cell so the drugs lose effectiveness,’ Professor Poulsen explains. ‘This protein, called an efflux pump, sits in the cell’s membrane, right beside the enzyme carbonic anhydrase. Without carbonic anhydrase controlling pH, the efflux pump stops working properly. This approach only targets cancer cells and effectively reverses drug resistance.’
As carbonic anhydrase inhibitors are effective at low doses, conventional chemotherapy doses might also be reduced, along with their side effects. This research was at the stage of early discovery and preclinical testing in late 2016.
Professor Poulsen explains the next steps for her research. ‘We are planning further tests to confirm the research’s potential. Assuming the results are positive, the next step would be IP protection and partnering with industry. All going well, the industry partner may take the candidate drug on to the next stage of testing, and ultimately commercial production and use in hospitals,’ she says.
Advancements in personalised medicine
As researchers and clinicians recognise what may heal one person may not work for another, personalised medicine grows in importance. The transformation of cancer care toward personalised medicine allows clinicians to select tailored treatments that can greatly improve chances of survival and quality of life. While clinicians rely on diagnostic tests to determine whether targets for the selected chemotherapy are present in the patient’s cancer, medical imaging agents used in hospitals are not very specific. GRIDD has developed an agent to identify cancers using Positron Emission Tomography (PET). A proof-of-concept imaging agent was able to differentiate those cancers with the drug target from cancers without that target. This research was published in late 2016.
Innovative technologies for new cancer treatments
GRIDD members led by Professor Vicky Avery are using a range of approaches to find new treatments for cancers including breast, prostate, pancreatic and ovarian.
Using innovative technologies incorporating 3D culturing techniques and high-throughput, high-content imaging, Professor Avery’s team addresses fundamental questions regarding the roles different cells play in the tumour microenvironment and how this relates to metastasis and drug resistance.
The team hopes to design improved chemotherapeutics to overcome limitations of many drugs used today and provide therapeutics for cancers for which there are no current treatment options.
Developing new technology platforms
The major objective is to develop model cellular systems, in both 2D and 3D, to investigate the tumour micro-environment and assess the impact that drugs and lead compounds have on different cancers, and determine cellular and soluble factors which influence drug efficacy. This knowledge allows the design of better drugs. The overarching goal is to provide innovative technology platforms to improve clinical predictability of lead compounds during early drug discovery.
Designing better drugs
Breast cancers
Breast cancer progression and metastasis often results in dissemination to the bone, thus cancer cells interact with a new microenvironment. These cells may remain quiescent for prolonged periods rendering existing therapeutics ineffective. Deciphering the milieu surrounding these cells in the bone microenvironment requires more detailed characterisation to improve drug discovery efforts. Building on our 3D imaging models, we are establishing new 3D models for metastasis to further our understanding of how the cells interact with one another, and the key factors that influence this. The more we understand about this environment, the more effectively we can design new drugs which target it.
Doxorubicin is a standard-of-care therapeutic for the treatment of breast cancer. Resistance to this drug occurs frequently, making it less effective against the cancer cells. Using advanced 3D cell models, we are investigating the mechanisms and factors within the tumour microenvironment, which reduce the effect doxorubicin has on breast cancer cells.
Prostate cancer
Metastasis to the bone also occurs with the advancement of prostate cancer. The specific factors surrounding this event and the establishment of the tumour in the bone have yet to be fully elucidated. Understanding the events which take place, and the role of the different immune cells in this process, will provide insights into how best to address and treat metastases.
We are exploiting small molecule libraries to identify new specific inhibitors against multiple different targets.
Cancer therapeutics
Professor Avery also heads the Queensland node of the Cancer Therapeutics CRC (CTx) based at GRIDD. The CTx mission is to discover new small molecules with potential for development into pre-clinical drug candidates, for the next generation of cancer therapies. The Avery team plays an integral role within CTx, providing expertise in molecular and cellular biology, high-throughput and high-content imaging capabilities for hit identification, and to support lead generation and optimisation.
Collaboration with the Translational Research Institute (TRI)
Associate Professor Rohan Davis has been working on prostate cancer research with Australia’s TRI since 2012. His team’s goal is to identify new, previously uncharacterised chemicals from nature that have an effect on cancer growth and metabolism. Unique natural product discoveries like this can form the foundation for drug development research, with intellectual property (IP) protection for subsequent translation and commercialisation.
A major component of the Davis team’s approach is chromatography, a chemical technique used to separate a mixture of chemical substances into individual components. This allows researchers to examine many different compounds present in plants, fungi and marine organisms. The team also applies analytic tools such as nuclear magnetic resonance spectroscopy and mass spectrometry, infrared spectroscopy and ultraviolet spectroscopy.
Potential to impact cancer treatment
The Davis team has recently discovered three novel and potent natural products from Australian biota that have unique mechanisms of action. These compounds inhibit or stop topoisomerase II and/or microtubule dynamics, which are validated cancer drug targets and have the potential to impact cancer research and future oncology treatments. Further studies are underway, with the intention of undertaking preclinical studies.
The team is also creating analogue libraries around specific bioactive natural products. This approach involves the semi-synthesis of 10 to 20 derivatives of each prioritised natural product compound and may lead to significant gains in potency in the drug discovery process. Should further research verify improved activity in the analogues, the next step is partnering with industry for clinical testing and commercial development.