Investigating the Spread of Cancer - RAH Research Fund
Centre for Cancer Biology 6 January 2016

Investigating the Spread of Cancer

Metastasis – the spread of cancers to secondary sites in the body is the main cause of death in many types of cancers including breast cancer.

In a bid to determine ways to stop this spread and ultimately reduce the numbers of lives lost, Adelaide researchers are looking closely at a protein in the body, which has been found to be mutated in many of the common cancers.

Conducted by the Cell Signaling Lab at the Royal Adelaide Hospital-based Centre for Cancer Biology, led by Adjunct Associate Professor Yeesim Khew-Goodall, this exciting project has the potential to lead to new therapeutic treatment for cancers.

“What we are working largely on is a protein, named Pez, that we identified quite a few years ago and found it was mutated in many of the common cancers,” A/Prof Khew-Goodall said.

“Around the same time we started noticing that different types of breast cancers have different amounts of this protein. Also the less severe forms of breast cancers, the ones that haven’t started spreading within the breast, actually have higher levels of this protein.

“The cancers that have started invading into the surrounding breast cancer tissue have lower amounts of this protein – and we now have some evidence that those mutations cause that protein to become non-functional, assisting the cancer cells to spread.

“We believe the protein’s normal job is to stop the cancer cells from growing, surviving and metastasising but for some unknown reason in some cancer cells, it’s either mutated, no longer functional or its levels are decreased so that its function is also decreased in those cells.”

A/Prof Khew-Goodall and her team have tested this idea in the lab and proven that the protein Pez does indeed act to suppress metastases.

‘We’ve proven this, but we can’t directly target the protein as a therapeutic – you can’t take a protein like this orally or inject it to restore its function. We also don’t want to stop this protein functioning, because that would make things worse,” A/Prof Khew-Goodall said.

“So what we are now trying to find is what is allowing mutated Pez to promote metastasis. We’re examining another group of proteins in the body, which we believe are what would actually be promoting metastasis in the absence of Pez.

“We now have all the clues and tools in place, to look for the actual drivers of metastases that counteract the action of the protein Pez.”

“Once we’ve nutted down to the most potent proteins that we want to target, we will look into finding inhibitors of those proteins – so we can stop them functioning.

“So for cancers that have low levels of Pez, or have mutated Pez, if we can inhibit the opposing proteins, we can rectify the situation.”

With this ongoing work, A/Prof Khew-Goodall says that the potential therapy that could be developed from these findings would need to be used in combination with other therapies.

“We don’t think that this protein mutation causes cancer, but it certainly does assist and promote the spread,” she said.

A/Prof Khew-Goodall believes it’s important for the community to be aware of these types of research projects, in particular to understand how important lab-based research is in the development of new therapies.

“Everyone thinks they’re invincible, but most people are touched by cancer in some way,” she said.

“I think it’s important for people to understand the work that goes into developing a new drug, it starts right here in the lab and is a very time-consuming exercise that requires the right amount of funding.

“I’m very passionate about this work and hope that one day it can contribute to stopping the spread of cancer – that would be quite amazing.