NSW cancer researchers shoot for the moon

NSW scientists are playing a key role in the US Cancer Moonshot initiative, which aims to make 10 years’ worth of progress in finding cancer cures in just five years, ushering in a new era of personalised medicine.

With an estimated 47,700 Australians dying from cancer in 2017 – that’s equivalent to 131 a day – it’s clear that accelerating the rate at which we find effective treatments is one of the most important things we can do for families across the country.

In recent years, treatments for cancers have advanced in leaps and bounds, but the fact that one treatment can be effective for some patients, yet have little benefit for others, has proven to be a significant hurdle.

Now, a massive Australian research effort has the goal of analysing 70,000 tumour samples from many different types of cancers. The result will be a database that allows doctors to match treatments to patients more effectively than ever before.

A revolution in oncology

Launched in 2016 at the Sydney’s Children’s Medical Research Institute (CMRI), the Australian Cancer Research Foundation’s International Centre for the Proteome of Human Cancer (ProCan) is working to revolutionise the diagnosis and treatment of cancer. 

The other half of the Australian Cancer Moonshot effort, at Sydney’s Garvan Institute of Medical Research, will look at cancer-causing defects in our DNA.

The Garvan Institute has the Southern Hemisphere’s largest facilities for studying the genome (the sum total of our DNA), while the CMRI is a leading global centre for analysing the range of proteins in our cells (the ‘proteome’).

The two initiatives have so far received a total of more than $50 million in funding to pursue their research in understanding how cancer works at both the cellular and molecular level, and they represent Australia’s contribution to the US National Cancer Institute’s US$1.8 billion-dollar Cancer Moonshot initiative.

Former president Barack Obama launched the initiative in his 2016 State of the Union address, harkening back to President John F. Kennedy’s 1962 call to get “a man on the Moon” by the decade’s end.

The ambitious project has been spearheaded by former US vice president Joe Biden, who lost his son Beau to cancer in 2015. He came to Australia to rally for local backing in 2016 and has continued to support Cancer Moonshot since leaving office, through the Biden Cancer Initiative.

Simple but staggering in scale

The concept of ProCan is simple but extremely ambitious, according to CMRI director and co-leader of the program, Professor Roger Reddel.

He says the results will greatly increase the speed and accuracy of diagnoses, making it much easier for clinicians to pick the treatments that are likely to succeed.

“ProCan will fill a major gap in our current knowledge of cancer, by analysing thousands of different proteins in tens of thousands of cancers of all types,” says Reddel, a University of Sydney professor of medicine.

“It will then use advanced computing to learn how to choose the best treatment for individual patients. Previously, it wasn’t possible to analyse cancer proteins on such a large scale.”

One example of how this can improve outcomes is in the treatment of breast cancer, Reddel explains.

If a tumour has a specific oestrogen receptor protein, there is a 70% chance that an anti-oestrogen drug will be an effective treatment. But some tumours don’t have this, causing one in three patients to endure unpleasant side effects unnecessarily.

“For the one patient that won’t respond, we aim to predict close to a zero percent chance of a response, which will help avoid a futile treatment,” he says. “For the other two women, we want to say they have close to a 100% chance of responding.”

A free, global database

Over the next five to seven years, ProCan will measure the precise profile – or proteome – of thousands of proteins in biopsy samples of cancers collected by researchers from around the world.

These profiles, as well as information about the treatment outcomes for those cancers, will be collated into a massive online library. While machines called barocyclers process tumour samples ready for analysis, a bank of specialised mass spectrometers then analyses them 24 hours a day, seven days a week.

“We have developed new methods to make it possible to operate these machines consistently,” Reddel explains. “The datasets we are generating are tenfold larger than from previous proteomic studies.”

The hope is to one day be able to generate a diagnosis and determine the most effective treatments for new patients within 24 to 36 hours of receiving a cancer biopsy.

ProCan has so far analysed the proteomes of nearly 10,000 tumour samples – an unprecedented number that is projected to double by the end of 2019.

The work at the Garvan Institute is coming at things from a different angle – sequencing the genomes of more than 1,000 people with rare, difficult-to-diagnose cancers called sarcomas.

Tumour samples from about 300 of these patients are being analysed for additional proteomic information by ProCan.

Sarcomas, which often have a genetic component and disproportionately afflict young people, are rare, but also “complex to diagnose, requiring great expertise,” says Professor David Thomas, who is leading the project.

It’s his hope that the work will reveal currently unknown genetic causes, and allow the researchers to develop not only new ways to diagnose sarcomas, but also create personalised programs to minimise the risk of genetic carriers going on to develop cancer.

“The fundamental goal is to map key molecular changes in cancer, from the genome to the proteome, and to make a critically important Australian contribution to the global effort to fight cancer,” says Anne O’ Neill, Director Enterprise and International Partnerships, NSW Office of Health and Medical Research.

“The aim is to make new treatments available for cancer patients faster.”

By John Pickrell