Prostate cancer is one of the most common forms of cancer, claiming the lives of around 3,000 men in Australia each year, yet not everybody who develops this disease is guaranteed either an early or accurate diagnosis of their condition.
The Prostate-Specific Antigen (PSA) test is the most frequently used tool to screen for prostate cancer, yet it can detect only certain types of tumours and is known to give rise to false negative and false positive results.
Earlier detection and more accurate prognosis of the condition is the goal of the potential life-saving research that UniSA’s Professor Doug Brooks is engaged in, and it is research that has secured a National Health and Medical Research Council (NHMRC) grant worth more than $1 million.
“It’s a large grant but we are also ambitious in terms of what we are trying to do, which is to revolutionise the field, in a way,” Prof Brooks says.
“It should allow us, for the first time, to diagnose patients accurately, and to enable them to be told whether they have prostate cancer, how advanced it is, and whether they need some radical intervention – at an early stage.”
With more than 30 years’ experience in medical research and expertise in developing practical applications in biochemical medicine, Prof Brooks is currently the leader of the Mechanisms in Cell Biology and Disease Research Group at the Sansom Institute for Health Research.
It is here that Prof Brooks’ research team is examining prostate cancer cell biology to find more specific biomarkers, with the ultimate aim being to provide better treatment plans for those diagnosed with this type of cancer, while easing the burden on the healthcare system which has seen patients misdiagnosed and being over treated in the past.
Prof Brooks says that the current PSA test, which screens for prostate cancer by measuring the blood level of PSA (a protein that is produced by the prostate gland), is not without fallibility.
“The higher a man’s PSA level, the more likely it is that he has prostate cancer. However, there are additional reasons for having an elevated PSA level, and some men who have prostate cancer do not have elevated PSA,” Prof Brooks says.
“PSA tests have a large number of false negatives and a large number of false positives and this can lead to over diagnosis and over treatment of patients, which is a big issue. The specificity of PSA is a problem – as it only detects certain types of tumours. PSA was originally developed only as a prognostic marker yet people have tried to apply it as a diagnostic marker.
“Our philosophy has been to take a step back and look at the cell biology and to see if we can find something that is consistently changed – in gene expression and protein expression – which gives us more specific biomarkers.”
It’s a step that has already yielded impressive results. Prof Brooks says that the endosome-lysosome system (a set of compartments inside cells) has a critical role in controlling protein secretion, making it an ideal system to identify new biomarkers that are released from cancer cells.
“We have discovered that the biology of endosomes (sub compartments of a cell which can also traffic things within cells) is significantly altered in prostate cancer and that endosome proteins have discriminatory capacity in cell lines and patient data sets,” Prof Brooks says.
“We’ve discovered that our biomarkers are more consistent, and more specific than current biomarkers. The whole biology of endosomes and the vesicular trafficking machinery that controls them is altered in terms of gene and protein expression.
“Interestingly the cell biology that we have discovered has an advantage over PSA.”
The next step – where the grant funding will be targeted – will be to analyse gene expression and to make antibodies and assays (to determine the amount of protein within a biological sample) to the endosome markers, so that tests can be developed and validated in model systems, and then adapted for use in patients.
“It will allow us to predict the course of the disease, and to predict which patients will go on to get aggressive disease and which ones will have indolent disease – so the medical community will have better markers for monitoring patients,” Prof Brooks says.
“They will know before a tumour gets aggressive or invasive, and the physician will be able to give patients that information and this will lead to more effective clinical interventions at proper time points; which means that treatments will be more effective, and resources are not wasted.
“The healthcare system will benefit and the patients should have improved outcomes and increased survival.”
UniSA PhD student Liping Wang has also been granted $83,429 postgraduate scholarship through the most recent NHMRC funding round to advance her research in the field of mechanobiology and mechanotransduction – the molecular mechanism by which cells sense and respond to mechanical signals.
Liping’s research will involve an experimental and computational study on the biomechanical behaviour of osteocytes which are the major type of bone cells embedded within the bone matrix, that regulate bone mass, bone quality and strength as well as bone repair outcomes.