Prostate cancer (PCa) is the most commonly diagnosed cancer among men in Australia and many other western countries. If treated early with surgery, PCa has a cure rate of over 90 per cent. However, once advanced, it is incurable.
Senior Lecturer and Head of the Translational Cancer Research Group in the Department of Medical and Molecular Biosciences, Dr Rosetta Martiniello-Wilks, has been researching PCa for the last 14 years.
“PCa occurs when the cells of the prostate begin to grow uncontrollably. If caught early, the surgical removal of the prostate can provide a cure. If left untreated, prostate cancer cells eventually break out of the prostate and invade distant parts of the body, producing secondary tumours (metastases) and making the cancer more difficult to treat.
“If the cancer has broken through the prostate capsule into the pelvis, this is called locally advanced PCa. If PCa has spread (metastasised) to distant organs and bone, it cannot be cured but merely controlled.”
Martiniello-Wilks’ words are grim, however she is confident her team’s latest research will provide viable treatment options for both advanced local and metastatic prostate cancer.
“Because of the high rate of advanced PCa disease, there is an urgent need to develop new treatments that can target and destroy cancer without harming healthy cells.”
Martiniello-Wilks with Professor Pamela Russell (formerly from Prince of Wales Hospital), CSIRO lead scientists Dr Gerry Both, Dr Peter Molloy, Dr Trevor Lockett and their laboratories, have developed a cutting-edge ‘direct delivery method’ for advanced local PCa. This Gene Medicine for PCa uses a unique and safe virus to deliver a suicide gene, in a targeted manner, to prostate cells. Clinical trials are due to start at Sydney’s St Vincent’s Hospital this year.
“Although the virus can infect all cells, the suicide gene is switched on in prostate cells alone and is then ‘activated to kill’ by the administration of a clinically approved prodrug into the patient’s blood stream. The prodrug is non-toxic to normal tissues that do not express the suicide gene. The suicide gene then converts the prodrug into a potent tumour-killing agent.”
For metastatic PCa, a second treatment method is currently under development. Here, adult bone marrow derived stem cells (BMSC) are used to deliver cancer-killing genes to metastatic cancer.
“These adult stem cells have three special properties which make this treatment possible. Firstly, they are attracted to PCa. Secondly, they are able to move through the body without being detected and destroyed by the immune system. Finally, they can be modified to carry cancer-killing genes.”
Once injected into the patient’s bloodstream, these gene-loaded stem cells will ‘seek and destroy’ PCa before they can spread any further.
For this treatment, BMSC are isolated from an individual and genetically modified outside the body in a highly-specialised facility. The BMSC are expanded to a therapeutic dose before reinfusion into the bloodstream of the same patient.
According to Martiniello-Wilks, BMSC are good vehicles for therapeutic gene transfer, “Largely due to their ability to seek out cancer anywhere in the body and their ability to evade rejection by the immune system, which is a major hurdle for most gene delivery mechanisms currently under investigation.
“Men die from metastatic prostate cancer, so better methods to combat it should show a greater impact on men’s wellbeing and, ultimately, survival.”
At UTS, Martiniello-Wilks and her team – Research Associate, Dr Jennifer Randall, Research Assistant, Mark Tan, and UTS Chancellor’s Research Fellow, Dr Nham Tran – are currently conducting therapeutic BMSC studies in mice with promising results. They believe it will be more effective and have fewer side effects than less targeted treatments.
In all her research, Martiniello-Wilks says collaboration is key. “This collaborative research has received funding from the National Health and Medical Research Council, Cancer Council NSW, Cancer Institute NSW, Sydney Cancer Centre Foundation, the US Department of Defence Prostate Cancer Research Program, the National Cancer Institute (in the USA) and commercial partners Mayne Pharma and Biotech Equity Partners to make the Gene Medicine for PCa a reality in the clinic.
“The BMSC work is currently generously funded by the Prostate Cancer Foundation of Australia.”
Research opportunities were also an important factor in her decision to come to UTS in January this year.
“I was attracted to UTS by the new priority to support internationally-competitive health research excellence and innovation,” says Martiniello-Wilks.
“Our research is facilitated by the Centre for Health Technologies (CHT) which is committed to the rapid translation of health research findings into clinical practice and policy. Professor Hung Nguyen and Professor Ann Simpson are co-directors of the CHT. The focus of the centre is the study of health and disease processes, the development and commercialisation of advanced biotechnology applications and new medical devices for early detection, diagnosis, treatment and rehabilitation of diseases including cancer, cardiovascular disease, diabetes mellitus and neurological disorders.
“I‘d like to think we’re doing cutting-edge work. If the BMSC work proves successful, this kind of treatment could be applied to a wide range of solid metastatic cancer types in the future.”
Marketing and Communication Unit
Photographer (R Martinello-Wilks): Joanne Saad
Bone marrow stem cell image supplied by: Rosetta Martinello-Wilks