Peter Mac researchers have received over $6.7 million in funding from the National Health and Medical Research Council to undertake innovative cancer research.

Some of the topics our researchers will be investigating include where cancer starts in two rare subtypes of ovarian cancer, how to stop cancer cells becoming immortal, and how genes become activated in metastatic castration-resistant prostate cancer.

In a very competitive funding environment, nine research projects administered through the Sir Peter MacCallum Department of Oncology at the University of Melbourne were funded in the latest NHMRC Ideas Grant round.

This represented a success rate of 17.6%, approaching double the national average of 9.8%.

Executive Director of Cancer Research, Professor Ricky Johnstone, says the success shows the quality of Peter Mac research.

“Every day our researchers are trying to better understand how cancers develop and evolve, in order to find new ways to treat them,” he says.

“This funding result shows our work is among the best in the country in developing innovative ways to improve the outcomes for people affected by cancer.”

Below are summaries of the research projects funded:

  • Dr Kristin Brown – Investigating the consequences of dysregulated lipogenesis in cancer

Reprogramming of cellular metabolism is a hallmark of cancer. As such, there has been growing interest in developing strategies to exploit metabolism for therapeutic gain. Our ability to do this is dependent on a thorough understanding of the mechanisms by which dysregulation of cellular metabolism contributes to tumour progression. In this project, we seek to investigate the fundamental mechanisms by which aberrant activation of lipid metabolism contributes to the tumourigenic process.

  • Associate Professor Kylie Gorringe – Discovering the cell of origin for rare ovarian cancers

Ovarian cancer has many different varieties, and even though they all grow at the ovary, for some types we don’t know the cell where the cancer starts. Using novel sequencing methods, this study will find the tissue of origin for two rare subtypes. This finding will help us to develop appropriate pre-clinical models that we can use to test emerging cancer therapies. Identifying the cell of origin will provide key insights into early detection or even prevention of these rare but deadly diseases.

  • Professor Ben Hogan – Growth factor directed developmental and pathological lymphangiogenesis

The formation of new lymphatic vessels occurs during normal development and in disease settings that include cancer metastasis and cardiovascular disease. We have now developed a sophisticated understanding of how lymphatics form in development but we understand far less about how they form in disease. This project will apply multidisciplinary approaches, including genetics, single cell genomics and computational biology, to directly compare how lymphatics form in development and disease. We hope to uncover new ways to manipulate this process for therapeutic gain.

  • Dr Brian Liddicoat – Understanding the role of DNMT1 SUMOylation in Acute Myeloid Leukaemia

Most cancers have abnormally high levels of DNA methylation, which turns off cell death genes, making cancer cells immortal. We are exploring drugs that will target this feature of cancer cells, which we believe will improve outcomes for patients with cancer.

  • Dr Ian Parish – Repurposing thalidomide derivatives to augment cancer immunotherapy

Immunotherapies are a revolutionary approach for cancer treatment, but most people with cancer do not respond to therapy. We have identified a new set of molecular switches that shutdown immune function and limit responsiveness to existing immunotherapies. Importantly, we have found a class of approved drugs that can block these immune “off switches”. This proposal will test if these drugs could be repurposed as a novel treatment to amplify the efficacy of existing immunotherapies.

  • Dr Anna Trigos – Understanding tumour plasticity and the microenvironment using single-cell technologies to identify novel targets for metastatic castration-resistant prostate cancer

Most prostate cancer patients respond well to treatment, but some develop metastatic disease and respond poorly. During metastasis the cancer spreads to multiple organs and new combinations of genes become activated, making it difficult to develop new treatments. We will investigate these patterns of activation of genes in metastatic samples and how the immune system interacts with the cancer. We will use computational models to identify new drug targets and evaluate immunotherapy as an option.

  • Dr Anna Trigos – Advancing the spatial analysis of cells in tissues to profile the tumour microenvironment

Tumours are composed of a mix of different cells, including cancer cells, immune cells and other cells supporting tumour growth. These cells are not organised randomly, but rather are distributed in specific patterns. Here we will develop computational methods to detect these patterns and determine what statistical tests should be used to compare samples. This project will give us the tools to investigate how the location of cells in tissues relates to treatment response and survival.

  • Dr Vihandha Wickramasinghe – Exploiting messenger RNA export as a novel therapeutic strategy to treat cancer

Novel therapies for cancers represent an area of unmet clinical need. We have identified a new biological pathway implicated in cancer, namely selective mRNA export. Compounds inhibiting other steps of the gene expression pathway are promising therapeutic candidates for cancer, yet mRNA export inhibitors do not exist. We propose to develop first-in-class inhibitors of mRNA export that selectively target transcriptionally addicted cancers with dysregulated RNA processing.

  • Dr Vihandha Wickramasinghe – Pathways that regulate nuclear export of circular RNA

An emerging and unusual class of RNA molecules, circular RNAs (circRNAs), is widespread and plays important roles in cancer initiation and progression. However, the pathways responsible for nuclear export of circRNAs are unknown. We propose here to systematically determine how circRNAs are exported from the nucleus and characterise the effect of modulating circRNA export pathways in cancer. This will enable us to determine whether circRNAs can function as a biomarker of patient response.