Our Venture Grants Scheme is designed to support cancer researchers who have courageous ideas that would not usually be funded by conventional research grant schemes.
This is the second time that Cancer Council has conducted the Venture Grants Scheme. Previous Venture Grants recipients have been able to prove their ambitious ideas and go on to attract funding from conventional sources. This would not have been possible without the backing of our donors who recognise that by supporting courageous thinkers we have the opportunity to uncover our future breakthroughs.
In order to fund the brightest minds, a competitive application and peer-review process was conducted in 2014 with the four successful recipients deemed to have met the following criteria:
The successful researchers will be known as Metcalf Venture Grants recipients to honour the late Professor Don Metcalf AC's commitment to and achievements in cancer research. Professor Metcalf was Cancer Council's Carden Fellow for 60 years.
Acute myeloid leukaemia (AML) is an aggressive blood cancer with more than 70 per cent of patients still succumbing to the disease. Recent research has uncovered recurrent mutations in proteins that help package and control the function of DNA within our cells - known as epigenetic regulators.
Mutations in these essential proteins appear to be an early and critical event in the initiation of AML.
Novel cancer therapies that target these epigenetic regulators have begun to emerge and previous work has also shown that drugs that target an epigenetic protein called BRD4 shows significant promise in animal models of AML.
Much like an unwanted shrub, most cancer therapies largely result in the pruning of the shrub, but it re-grows as the roots that sustain it are unaffected.
Our ability to develop treatments that eradicate leukaemia stem cells (LSC), which are at the root of this form of leukaemia, has been hampered by the fact that that they are difficult to identify and it has not been possible to grow them effectively in the laboratory to study them.
This research team has recently identified a unique method to grow large quantities of LSC indefinitely in the laboratory. This discovery will enable them to study these cells and identify what the major epigenetic regulators are that sustain and perpetuate them. They will use cutting-edge genetic technology specifically to reduce the levels of individual epigenetic regulators to assess if this impairs the survival of the LSC.
They will then work on identifying the region of the protein that they need to design drugs against that will eradicate LSC.
"Only by peering into the mechanics of cancer initiation and progression will we uncover frailties that may lead to therapeutic progress." - Associate Professor Dawson
Professor Roger Daly, Professor Vinod Ganju, Cancer Council's Colebatch Fellow Associate Professor Sherene Loi, Associate Professor Kaylene Simpson, and Professor Christina Mitchell.
Monash University, Peter MacCallum Cancer Centre and the Victorian Centre for Functional Genomics.
Triple negative breast cancer (TNBC) is a highly aggressive subtype of the disease that constitutes up to a third of breast cancer cases. It presents a major clinical problem due to its aggressive nature and because targeted treatments suitable for other forms of breast cancer are ineffective. At the moment, the only drug treatment that can be given is chemotherapy, which often has harmful side effects.
While it is becoming increasingly evident that not all TNBCs are the same, we do not understand the molecular basis of these differences. Therefore, we do not know how to treat TNBC patients in a personalised fashion, so that they each receive optimal treatment.
This research team hypothesises that there are different subclasses of TNBC, each exhibiting characteristic changes in chemical signals and kinase activity. If this is correct, then measuring these signals and activities represents a novel way of sub-classifying TNBC. If they can identify the kinases in each subclass that generate key growth-promoting signals, then these kinases represent potential therapeutic targets, which would be a major step towards personalised treatment.
To do this they propose to use cutting edge approaches to measure the chemical signals and kinase activities present in TNBCs. In a world first, this will enable them to subclassify the cancers according to the signals that are present, and identify the kinases that emit these subclass-specific signals. This will lead to improved treatments, and ultimately to reductions in morbidity and mortality.
"We want to identify new personalised treatments by advancing molecular sub-classification of triple negative breast cancer - a world first." - Professor Daly
Professor Ricky Johnstone, Dr Jake Shortt, Dr Philip Thompson, and Professor Miles Prince.
Peter MacCallum Cancer Centre and Monash Institute of Pharmaceutical Sciences.
Multiple Myeloma (MM) remains an incurable blood cancer with almost 1500 Australians diagnosed each year. While treatment options for MM patients have improved with the development of new therapies such as immunomodulatory drugs (IMiDs), there remains an unmet medical need for new treatments.
This project aims to discover new proteins and pathways necessary for the growth and/or survival of MM cells that can be targeted to overcome IMiD resistance. The second part is based on a startling discovery made last year showing that N-methy-2-pyrrolidone (NMP) which was long regarded as a stable and inert solvent affects the growth and survival of MM cells. This team will now try to identify novel NMP-binding proteins as therapeutic anti- MM targets.
To do this they need to identify which proteins MM cells rely on for their growth and survival.
Using state-of-the-art gene knockdown technologies available at Peter Mac, they will deplete human MM cells of each of the 200 proteins degraded following IMiD treatment and determine if the cells die or stop growing. These screens will provide the researchers with a unique way to identify new targets for the development of novel anti- MM agents.
Following this, they will then partner with chemists and other drug-development experts to develop new anti-MM compounds for testing in the laboratory. They also hope to expand on previous work done on an organic compound known as NMP to develop analogues that will be more potent against MM cells.
These studies will allow researchers to better utilise NMP and related compounds and will provide a drug development pipeline essential for the production of better, more potent anti-MM agents.
"This entire project is blue sky, risky and highly ambitious. However, should we be successful in discovering biologically important targets, thousands of sufferers of multiple myeloma around the world will be the beneficiaries." - Professor Johnstone
Professor Andreas Strasser, Dr Marco Herold, Professor, Jane Visvader and Professor, Geoffrey Lindeman.
Walter and Eliza Hall Institute of Medical Research.
One of the reasons why cancer mostly occurs in older people is that the body possesses so-called ‘tumour suppressive' processes that prevent the development of malignant tumours. The process of tumour development is called ‘neoplastic' or ‘malignant' transformation of cells. The tumour suppressive processes result in the killing of cells that are abnormal and in the process of becoming transformed, or prevent the multiplication and spread of these abnormal cells.
While we have a basic understanding of some of these tumour suppressive processes, and some regulators of these processes (so-called tumour suppressors) have been identified, several have not.
This is at least in part because until recently there was no efficient way to look for and discover these tumour suppressors.
An exciting technology (CRISPR/ Cas9 genome editing) has recently been developed, which is ideally suited to discover tumour suppressors. A member of this team, Marco Herold, was the first to establish its routine use in Australia and has improved it so they can perform large-scale screens to identify novel regulators that prevent the development of cancer. This project will use several experimental mouse models for leukaemia, lymphoma and breast cancer and will then investigate the biological functions of likely tumour suppressors that will be uncovered in the screens.
The results from the proposed screens and follow-up investigations will have major impacts for future cancer research.
The team expects to identify novel processes that suppress tumour development and the critical regulators of these processes, which will lead to improved strategies for cancer therapy.
"We want to discover mechanisms that impose breaks on cancer development and expansion of malignant tumour cells in order to develop new therapies." - Professor Strasser
Contact Anthony North to discuss how you could ‘Be there at the Breakthrough' by supporting our Venture Grants Scheme. Email firstname.lastname@example.org or call 03 9514 6513.