Almost 10 years ago, my research group and I started studying proteins in cancer cells that we thought may prove to be targets for cancer therapy. We couldn't have predicted the incredible discovery we were about to make.
It began with a cell surface protein found to be present in most cancers, called Fn14. We expressed Fn14 in tumours, which we then implanted into mice. We noticed that as the tumours grew, there was massive weight fluctuation, caused by muscle wastage and fat loss (these symptoms are called cachexia in cancer patients).
The mice lost 10 percent of their body weight every day. After scratching our heads for a while as to why this was happening, we realised we'd made a huge discovery.
Previously it was thought cancer itself caused the muscle wastage disease known as cachexia, however, we confirmed this wasn't so. It was actually caused by the Fn14 molecule in cancer cells.
Cancer-induced cachexia is a muscle-wasting disease that kills up to a third of all cancer patients. Between 50 and 80 percent of people with solid tumours (particularly those with very aggressive cancers such as pancreatic or colorectal cancer) suffer from this wasting condition. Because cachexia causes emaciation and weakness, it can mean patients aren't always strong enough to continue harsh cancer treatments like chemotherapy.
It causes loss of body weight, which is seen in many advanced cancers -- as well as other diseases such as HIV, tuberculosis and Type 1 diabetes. Cachexia manifests as muscle loss, fat loss and overall metabolic imbalance. When you lose muscle mass, your immune system becomes weak and you lose the ability to even do simple things like walking.
Once we knew the cause of cachexia, we created an antibody that can block the action of this molecule on a tumour -- a "magic bullet" if you like. This magic bullet is very specific -- it targets the Fn14 molecule and turns it off. That means side effects would be less severe than accompanying chemotherapy drugs, which block cancer cell growth, but also affect normal cells from dividing.
Making this discovery -- and then creating the antibody to target cachexia -- is truly exciting. It knocked us over really. We were so excited about what we'd found, and how it might help people in the future.
My only regret is that we didn't discover it ten years earlier. I retired two years ago, but came out of retirement this year so I could see this research through to a point where we can get our discovery in to initial clinical trials in humans and licenced to a pharmaceutical company for international trials, then we have hope it will get into clinics. It's truly a joy to go to work every day, because I work with a team of people who are devoted to getting answers. How lucky am I?
Our work so far deals only with cachexia caused by cancer, but cachexia is also associated with ageing. It just goes by a different name -- sarcopenia. Muscle wastage is one of the biggest factors in older people having falls and generally becoming immobile from muscle wasting. What if we could successfully create a treatment for this? The thought is almost overwhelming.
We're in the process of finding investors to help us fund the research. Funding is always hard as this sort of research is lengthy and every experiment can bring a surprise. But it's by having a committed team of excellent researchers, being persistent and getting answers that only have one possible explanation that you can make incremental steps forward. At the moment, our antibody drug isn't ready for humans, but we want to get it into human trials within the next four years.
If we can help block cachexia, patients would keep their strength up and be able to continue cancer treatment. It would increase their quality of life -- and their life expectancy. If a patient's state of mind is good, and they feel well, it can be a huge influence on the outcome of a disease.
As a Biochemistry Professor, one dreams of making a discovery like this.
Learn more about how La Trobe researchers are solving the big issues of our time.