Chasing a cure for cancer
SAI NARAYAN on a UWS scientist’s life-long research
Cancer is a leading cause of death in Australia – more than 43,000 people are estimated to have died from the disease in 2010. 1 in 2 Australians will be diagnosed with cancer by the age of 85. An estimated 114,000 new cases of cancer were diagnosed in Australia in 2010 alone.
Many of us know someone in our own or extended family who has been afflicted by this terrible disease. My grandmother died of blood cancer even before I was born. My aunt has been fighting cancer with tremendous courage for the last four years and her own words after her diagnosis in 2007 were, “Pain, tension, fear, hope and worry became our constant companions.”
Research is the key to finding answers to our questions about cancer – what causes cell damage, why cells turn cancerous, how cancer grows and spreads, and how we can most effectively attack it. Eminent researcher Professor Arun Dharmarajan of the School of Anatomy & Human Biology, University of Western Australia , is leading the fight against cancer through his path-breaking work. His most significant finding is that a naturally occurring protein – secreted frizzled-related protein 4 (sFRP4) – inhibits tumours by blocking off the blood supply containing the oxygen and nutrients they need to survive. Prof Dharmarajan is also recruiting an “army” of some of India ’s top young students to join UWA medical researchers in battling this disease.
Indian Link spoke to this modest, unassuming, but highly respected and driven scientist and medical researcher, who hopes to make a positive difference in the lives of innumerable cancer patients.
Sai Narayan: What motivated you to come to Australia and make Perth your home?
Prof Arun Dharmarajan: I was born in India near Trichy. My family migrated to Sri Lanka when I was five. At fifteen, I returned to India to do my pre-university schooling, followed by bachelor’s degree in science and post-graduation in human physiology, anatomy and biochemistry at the University of Madras . I returned to Sri Lanka as a lecturer at the University of Sri Lanka , but I felt that research was my true calling. I started reading research papers and my PhD mentor Professor Neville Bruce’s paper – he was based here in Australia – fascinated me. He was working on research on the corpus luteum – an organ formed every 2 weeks at the time of ovulation. It usually lives for 2 weeks and dies. But during pregnancy it lives for 3 months. The fate of the organ is decided at the time of ovulation – 2 weeks or 3 months. In his paper, he asked the question: “What determines the life of this organ?” I wrote to him in 1980, asking if he could take me on as a PhD student. I persevered and applied for a scholarship which was granted. I landed in Perth and started working with Prof Bruce, and published many papers with him. After my PhD, I did a ten-year stint at the John Hopkins Medical School in Baltimore , USA where I steadily rose up the ranks. But when Prof Bruce advised me to return to Perth , I came back.
SN: Do you still maintain links with India ?
AD: I go to India 2-3 times a year, mainly because I initiated the ‘ India only’ scholarship at UWA in 2007-2008. We secured 50 PhD scholarships (across all disciplines) at UWA just for India . I visit different institutions – research and universities – to tell them about UWA and the scholarship scheme. Nowhere in the world has any university awarded 50 scholarships dedicated to India .
SN: How did you get started with cancer research?
AD: I started by trying to find out what was telling this organ – the corpus luteum – to die. There is a phenomenon called programmed cell death. When animals are pregnant the corpus luteum lives for bit longer and continues to do its job. That prompted me to find out what causes this organ to live or die. I went to the cellular level and started finding genes that are expressed at the time of death. As a natural extension, what happens in cancer is that the cells don’t die. They become resistant to death and even chemotherapy can’t kill them. I moved on to cancer research. What interested me most was chemo resistance. Ovarian cancer cells become resistant to chemo. So what was different about these cancer cells? I found a few genes over-expressed in these tumours. If these genes are suppressed, then treated, they can be killed. They become chemo sensitive. About 5 to 6 years ago I found a particular protein I have been working on for the last 17 years, which can block blood supply. We used cell cultures in special mice called “nude mice”, they are immune deficient and cannot reject a foreign body. We injected human ovarian cancer cells in these mice. Then we injected the protein we discovered and looked at the tumour volume over time. The tumour never grew, whereas in the control mice the tumour was very aggressive, visibly seen. We measured this for 45 days; the protein totally suppressed the tumour growth! If we cut off the blood supply, it cannot survive. If humans don’t get food, they can live on for some time but eventually they will perish. It is the same with the tumours. Cut off the blood supply and eventually they will die. They cannot grow. The protein does this. But research is never-ending and we have to find out how the protein prevents tumour growth. I am currently exploring these mechanisms.
SN: So when did you start considering this protein for commercialization?
AD: This discovery about cutting off the blood supply with SFRP4 is only 5 years old. It takes about 10 years from bench to bedside! We still have to conduct toxicity studies, that’s where nanotechnology comes in. Before we can start Phase 1 clinical trials on humans, we have to fully ensure it is not toxic. For our patients, we have to ensure that all other organs are fine; imagine if it cuts off the blood supply to the brain or heart while suppressing liver cancer? Several companies Pfizer, Johnson and Johnson, Amgen have indicated that their concern is (targetted) delivery.
SN: How is nanotechnology being used in your research?
AD: Nanotechnology can encapsulate this protein into a very small particle. You can coat the surface of this particle with a signalling molecule that can recognise the tumour and reach it, in order to break it. Because of the difference in pH, it can go near and bombard the tumour and when it does that, the protein is released and it can act on the tumour.
The second thing is that it’s a big protein. What we were working on is to try and break it into very small fragments. I have been able to accomplished that. We now encapsulate this small protein using nanotechnology to target the tumour. It can do targetted drug delivery.
The concern with nanotechnology is that the particle we are using to encapsulate it should not be toxic itself. That’s a major reason why people have not used nanotechnology in human patients yet. It is still at the animal level. Leave alone the protein, the particle used to encapsulate has to be totally toxin free.
SN: How far off are you from clinical trials on humans?
AD: 2-3 years, I’d say. Pharma companies want us to do some additional validation before taking it through Clinical Trials 1-3 and to the market.
SN: Which Indian labs are you collaborating with?
AD: On this project, we are working with Anna University in Chennai. It’s a joint patent between Anna and UWA that has been going extremely well over the last 5 years.
SN: What are your major goals for the next 5 years?
AD: I want to take this discovery to the market. If it doesn’t help extend life I won’t be satisfied.
SN: How do you balance between work and home in your field of scientific research?
AD: I appreciate my wife and son’s support. It’s a 24 hour job. I travel extensively – for about SIX months in a year. Family support is very important to science research. My wife Bawani is a diabetic and has been for 20 years and so it’s difficult for her to travel, but you wouldn’t know it if you saw her. In my PhD thesis, I thanked her for being a “scientific widow”! Sometimes we don’t even see each other for three-four days. I come home at midnight and leave early in the morning, it has become a routine.
