A clinical trial to prevent breast cancer in high-risk women, projects to identify potential new cancer therapies and gene silencing were among those funded today by the Australian Government.

Walter and Eliza Hall Institute researchers received more than $26 million in Australian National Health and Medical Research Council (NHMRC) project grant funding in the latest grant round, announced today.

At a glance

• The Institute received more than $26 million to fund 27 projects, a success rate of 29 per cent.
• A $2.6 million grant will fund the first international study to prevent breast cancer in women with a faulty BRCA1 gene.
• $1.5 million will fund research to uncover how genes are silenced, while another $1.8 million will support the search for new cancer treatments.

Preventing breast cancer

Breast cancer researcher Professor Geoff Lindeman and his team received almost $2.6 million for the first international study to prevent breast cancer in high-risk women.

The BRCA-P clinical trial will test whether the drug denosumab could safely and effectively reduce the incidence of breast cancer in women with a faulty BRCA1 gene. These women have a 70 per cent lifetime risk of developing breast cancer.

The randomised phase 3 trial will recruit women with the BRCA1 mutation, who are aged 25 to 55, and are breast and ovarian cancer free. The trial will be run in Australia by Breast Cancer Trials.

Professor Lindeman, who is also a medical oncologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, said the clinical trial was based on more than a decade of basic and translational research into the biology of breast cancer.

“Together with Professor Jane Visvader, our laboratory at the Institute has focused on understanding how normal breast cells grow and develop in order to understand what goes awry in cancer,” he said.

“One strand of this research culminated last year in a study that showed the RANK ligand inhibitor denosumab represented a possible new prevention therapy for women with a faulty BRCA1 gene.”

A pilot study is being performed in collaboration with the Royal Melbourne Hospital and Victorian Comprehensive Cancer Centre.

“The only proven preventive measure available to women with BRCA1 mutations is a double mastectomy, so new strategies are urgently needed. With this funding, we will be able to determine whether we can safely and effectively prevent or delay breast cancer in this ‘high-risk’ group.”

Unmasking the secrets of gene silencing

Associate Professor Marnie Blewitt received almost $1.5 million to further her research into the epigenetic control of gene silencing, with colleagues Dr Matthew Ritchie and Dr Andrew Keniry.

Epigenetic marks are changes made to the DNA which help genes to be switched off in some cells and switched on in others, for example the gene for elastin to be switched on in skin and off in blood.

Associate Professor Blewitt said epigenetic marks were critical to normal development and, when disrupted, could drive a range of diseases.

“We are interested in the genes that are necessary to add epigenetic marks to the DNA and understanding how the many genes involved in this process cooperate at the molecular level to switch genes off,” Associate Professor Blewitt said.

“Using X-chromosome inactivation as our model, we will use unique screening technologies to look for new epigenetic modifiers and mechanisms critical to gene silencing.”

Searching for new cancer therapies with CRISPR

Dr Marco Herold is the lead investigator on two NHMRC grants, receiving more than $1.8 million to identify new ways of treating cancers, including acute myeloid leukaemia, lymphoma and other cancers. The team includes Professor Andreas Strasser, Dr Ian Majewski, Dr Marie-Liesse Asselin-Labat and Dr Wei Shi, as well as Dr Andrew Wei at the Alfred Hospital.

Dr Herold leads a laboratory using sophisticated CRISPR technology to quickly and efficiently modify the genetic code. Dr Herold said his team is using CRISPR to study genes that may play a role in either activating or suppressing cancer development and growth.

“In one of the projects, we are looking at a gene called p53, which is mutated in around 50 per cent of all human cancers, rendering cancer cells immune to many widely-used anti-cancer treatments," Dr Herold said.

“Understanding the cellular responses that are essential for p53-mediated tumour suppression and p53-driven responses of cancer cells to anti-cancer therapeutics will allow us to identify attractive novel targets for cancer therapy.”

A tremendous outcome

Institute director Professor Doug Hilton said he applauded the efforts of the Institute’s researchers and staff in securing successful funding.

“I think it is a tremendous outcome and something about which we should be rightfully proud,” Professor Hilton said. “Among those are many tremendous projects about which I, and many senior people at the Institute, are excited. Continued government funding of medical research is essential for us to continue to undertake research that will deliver health benefits to the community in the future."

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