These findings could translate into huge benefits for those fighting serious illness and the potential for effective treatment is now much closer to reality.
Nick Hoogenraad, Professor of Biochemistry

For many years, oncologists and researchers thought the dramatic weight-loss of cancer patients was due to the cancer spreading through and consuming the body, with the loss of appetite and nutritional complications causing the body to waste away. But in fact, it’s cachexia, a severe weight loss and muscle wasting disease often devastatingly present in cancer’s later stages.

Since cachexia was identified, the next challenge for researchers has been to work out what causes it. The credit for a recent discovery goes to a 28-strong research team from Department of Biochemistry and Genetics at the La Trobe Institute for Molecular Science in Melbourne, led by Dr Amelia Johnston.

But it wasn’t so much a ‘eureka moment’ as a surprising observation about the behaviour of a particular molecule, Fn14, that had to be tested and proved over months and months.

Game-changing research

Back in 2007, biochemist and cell biologist, Dr Johnston was a postdoctoral researcher. Together with her colleagues, they set out to learn more about the behaviour of Fn14, a molecule that is generally absent in a healthy body, but often present in a tumour state.

What they discovered was that when Fn14 was expressed on the surface of cancer cells, it caused cachexia. It’s a world first.

From left to right: Professor Nick Hoogenraad, Laura Jenkinson and Dr Amelia Johnston

“It wasn’t a ‘Wow! Look what we’ve got!’ moment; more of a ‘Goodness me, what’s going on?’ Once we worked it out, it was mind-blowing. We spent months double and triple checking our hypothesis, and the result was always the same; the models with Fn14 lost weight, muscle tone and overall suffered deteriorating health” recalls Dr Johnston.

Over the following decade, they developed a way to halt the advance of cachexia with an antibody treatment.

Cachexia’s symptoms include weight loss, muscle wasting, loss of tissue and decreased strength. It is present in 50 to 80 per cent of cancer sufferers with solid tumours. In cases of advanced cachexia, cancer treatment is often withdrawn due to a person's emaciated state, and experts estimate that as many 30 per cent of cancer deaths can be attributed to the presence of cachexia.

“We began to test antibodies on the Fn14 in tumours and observed the symptoms of cachexia dissipating. It was extremely exciting,” says Dr Johnston.

La Trobe’s discovery that Fn14 can cause cachexia brings researchers closer to finding a way to stop cachexia in cancer sufferers and may have the potential to help fight cancer directly. In some cases, treatment with the 'antibody' therapy that blocked the cachexia also slowed the growth of the tumours.

CLICK TO PLAY VIDEO: A story of cancer, discovery and fighting back.

Cancer touchstones in the real world

“If you've ever known anyone that's suffered from cancer and had cachexia you’ll know how debilitating and demoralising the condition is, not only for the patient but also for the families involved,” says Dr Johnston.

“I know people who’ve been unwell with cancer-cachexia and watched them go through those challenges. I’ve seen somebody waste away in the last few months of their life. It’s so difficult, and having those personal stories to come back to, drives us to do what we do.”

“These findings could translate into huge benefits for those fighting serious illness and the potential for effective treatment is now much closer to reality. If we can arrest cachexia it will give people extra time, improved quality of life, make them stronger and allow for therapy to continue,” adds Professor of Biochemistry, Nick Hoogenraad, who also leads the team with Dr Johnston.

The La Trobe Institute for Molecular Science (LIMS) is committed to solving global problems and improving the welfare of human societies.

Explaining the science

Fn14 is a receptor on a cell's membrane that is often present on cancer cells. It’s usually absent on healthy and normal tissue, although it does play some beneficial ‘repair’ roles in the body like developing new muscle tissue, and helping the process of wound healing.

“When the body uses Fn14 in this way, it’s switched on to do its job and then switched off by the body when the job is finished,” explains Dr Johnston.

“Unfortunately when Fn14 is present in a tumour setting, it’s switched on and remains switched on, enabling the tumour to thrive. The tumour cells then send disruptive signals to the rest of the body, and it's these signals that are responsible for causing the muscle wasting and the other symptoms of cachexia.”

Watch Dr. Johnston and Professor Nick Hoogenradd explain her research.

Dr Amelia Johnston

From the laboratory to the clinic

Real-life outcomes are always on the agenda for research teams like the one behind this stunning discovery.

“We started to wonder, 'What if we could translate our findings to humans and develop a therapy that could treat and block the cachexia symptoms in cancer patients? What if we could give back quality of life to cancer patients suffering from cachexia?'” says Dr Johnston.

The team has been able to generate an antibody therapy that can block Fn14, and then block cachexia. The next step is to develop an equivalent treatment that is suitable for use in humans.

To achieve this, La Trobe University has partnered with Professor Andrew Scott of the Olivia Newton-John Cancer Research Institute, which is also in Melbourne. The teams are working closely together to further this research, and clinical trials are expected to begin in two to three years.

Although research is still early stage with no guarantees it will translate into a comprehensive treatment, the teams hope stopping cancer-cachexia in its track it will give cancer sufferers extra time, improve their quality of life, and make them strong enough to enable their cancer treatment to continue — and be successful.

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