Unlocking secrets to cancer spread

BEE venom and seas sponges are the unlikely sources of two innovative approaches to cancer treatment being developed in Western Australia.

They are among many ideas in development at several public and private WA organisations to target one of the country’s leading causes of death.

Cancers make up seven of the top 20 causes of death nationally, according to the Australian Bureau of Statistics, and on average kill Australians earlier than any other cause except suicide and cirrhosis of the liver.

Thirty years ago, only five in 10 Australians diagnosed with cancer survived more than five years after their diagnosis.

By 2019, that number had increased to around seven in 10.

Cancers of the lymphoid and haematopoietic tissues, affecting the blood, bone marrow, lymph and lymphatic system, killed Australians at a rate of 15.2 per 100,000 people in 2019, according to the ABS.

The rate in WA was lower, at 13.6 per 100,000 people.

These cancers are among those targeted by Perth Blood Institute, one of several public and private WA organisations researching how cancers work and how they can be treated.

PBI runs clinical trials into blood and bone marrow diseases including leukemia, lymphoma, myeloma, haemophilia, and deep vein thrombosis, led by the institute’s founding director, consultant hematologist Ross Baker.

One trial tested a class of drugs called BTK inhibitors, which work by binding to and inhibiting Bruton’s tyrosine kinase, an enzyme important in cancer cell proliferation.

It’s a step away from previous treatments for the disease: the heavy-duty chemotherapy of the past that was less targeted and came with severe side effects.

“Traditional chemotherapy affects all blood cells, the good ones that we all need and also the cancerous cells,” Professor Baker told Business News.

“The new therapy’s effectiveness is much better because you’re really targeting what’s gone wrong rather than putting a blanket over the whole body and hoping the good cells will come back.”

This approach was successful with cancer patient John Coccaro.

In 2006, Mr Coccaro was diagnosed with chronic lymphocytic leukaemia, a cancer that attacks blood and bone marrow.

Since then, Mr Coccaro has spent years in and out of hospital undergoing chemotherapy. Every time doctors thought they’d beaten the disease, the cancer returned.

After taking part in the trial of BTK inhibitors, Mr Coccaro is touring northern Australia in a caravan with his wife, having been cleared of any trace of the cancer in his blood.

Honeybee venom is being used in another project. It is exciting researchers because of its ability to target cancer cells directly and kill tumours.

The venom’s potential has been known to researchers since the 1950s when it proved successful in stunting the growth of tumours in tomato and wheat plants.

Now, University of Western Australia researcher Ciara Duffy has isolated the active compound in the venom.

Known as melittin, it’s a small, positively charged protein that targets cancerous cells, particularly the most aggressive HER2-positive breast cancers, and creates holes in the cell membranes.

Andrew Redfern is an associate professor of medical oncology at the Harry Perkins Institute of Medical Research and a clinical adviser on the project.

He said melittin had great potential not just on its own, but also in conjunction with more traditional cancer treatments.

“It’s basically putting a porthole into the cancer cell membrane, and then drugs can get into that porthole,” Dr Redfern said.

“This porthole activity, so to speak, is quite nifty.

“We found that when we gave melittin and gave docetaxel, which is one of the most active breast cancer drugs that we use normally, that the docetaxel is more effective against cancer.”

At the Breast Cancer Research Centre WA, one of the state’s busiest cancer trials units, 57 per cent of their trials focus on metastatic (stage 4) breast cancers.

BCRC WA researchers are investigating how metastatic cancers respond to treatments, and why some don’t.

A class of drugs called CDK inhibitors is used to treat advanced breast cancers, limiting the spread of the disease to extend the lives of patients as long as possible.

Researchers noticed that resistant cancers used a process called epithelial mesenchymal transition (EMT) to circumvent the effects of the CDK inhibitors.

Preliminary research shows that a well-known cancer drug, generically known as eribulin, a synthetic analogue of a chemical produced by sea sponges, may also inhibit the EMT pathway.

By comparing samples of tumours before and after they metastasised and taking into account the treatments each woman was given, researchers hope to be able to predict which treatments will be most effective for each patient.

“Knowing what not to give patients is just as important as knowing what is good to give to them,” BCRC’s education and liaison manager, Linda Armstrong, said.

Besides new ingredients and methods, researchers are also looking into the impact of demographics on cancer survival rates.

Breast cancer is the most commonly diagnosed cancer in Australia, but over the past 10 years it’s slipped down the rankings from 12th to 15th most common cause of death, killing women at a rate of 17.8 deaths per 100,000 people. In indigenous women, those statistics are less encouraging.

Though they’re not as likely to be diagnosed, Aboriginal women are twice as likely to die from the disease as the general population.

In WA, the statistics are calculated more precisely and show a three-fold impact.

Dr Redfern’s work on breast cancer in indigenous women has overturned the traditional narrative about why indigenous women are at such high risk.

“There’s been an assumption that it’ll be cultural and geographic and that [indigenous] people are coming further, are more reluctant to attempt treatment, have a lower belief in treatment or things of that nature,” Dr Redfern said.

After a survey of every case of breast cancer in indigenous women over the past 20 years, Dr Redfern found indigenous women were far more likely to be diagnosed with the most aggressive forms of breast cancer, HER2 positive and luminal B.

Nutritionally, Aboriginal people have been found to typically have lower vitamin D levels, making their cancer more aggressive and difficult to control.

They’re also more likely to experience greater side effects from treatments and are more often taken off any given treatment because of those side effects.

Dr Redfern said the breadth of the differences took researchers by surprise.

“We thought we might get a couple of hits; we’ve had some ideas about what we know can be different across cancer results, and we thought that there may be a couple of them in indigenous women, but we didn’t think it would be all of them,” he said.