The vision for a cancer research powerhouse in Melbourne has received a significant boost with the announcement of the National Health and Medical Research Council (NHMRC) grants by the Australian Government.

Peter MacCallum Cancer Centre has been awarded $13 million for major cancer research projects and fellowships aimed at identifying better treatments, better care and potential cures for cancer.

Executive Director Cancer Research Professor Joe Trapani said researchers are continuously uncovering new ways to combat the killer disease which claims the life of more than 45,000 Australians every year.

“These grants support new and cutting-edge research designed to control the impact of cancer in our community. The work also contributes to global advances in how cancer is understood, diagnosed and treated,” Professor Trapani says.

“Research is making a real difference. We can now super-charge a patient’s own immune system to fight cancer. Genetic information is being used to prescribe medicines that specifically target the mutations that cause certain cancers, and we are developing new ways to detect the spread of cancer.

 “What’s fantastic about many of these grants is they support research that is designed to translate directly into better cancer treatments and care for all people affected by cancer in areas such as blood, lung, breast and ovarian cancer, together with the ground-breaking field of cancer immunology.”

Three grants were awarded to Early Career Researchers, totalling more than $1.5 million. Professor Ricky Johnstone, Associate Director Laboratory Research at Peter Mac, says it is rewarding to see the work of young cancer researchers being supported through the grants program.

“This type of investment, coupled with the facilities we now have in the VCCC building, is helping to retain some of the brightest minds emerging from our education system, while also serving to attract the very best cancer researchers to, or home to, Australia,” Prof Johnstone says. 

A feature of many of the grants awarded to Peter Mac researchers is that the funded projects are likely to directly impact on cancer patients in a variety of ways. Here are some examples of grants supported by NHMRC in 2016:

Preventing infections, saving lives
A Peter Mac team will lead a new Centre for Research Excellence focused on managing infections which affect many cancer patients who are severely immune-compromised due to the disease or the associated treatment. The team will investigate areas such as infection surveillance; sepsis and neutropenic fever. They aim to establish new research networks to detect emerging multi-resistant infections, develop guidelines on how to manage them, implement successful programs that have been shown to save lives internationally and validate new practice changing immune, bioinformatics and diagnostic technologies. Chief Investigators: Prof Monica Slavin, Prof Karin Thursky and Assoc Prof Leon Worth.

A new paradigm for targeting mutant p53 tumours
Over half of all cancers contain mutations in a gene called TP53, also known as the “guardian of the genome”. Mutation of TP53 provides tumour cells with a growth advantage, and leads to resistance to chemotherapy and poor outcomes for patients. Professor Phillips and his team have identified a potential “Achilles’ heel” in cancers with TP53 mutations. This research is designed to establish a new paradigm for treating tumours with TP53 mutations that will be applicable to a large number of patients across all types of cancer. Chief Investigator: Prof Wayne Phillips.

Mechanisms of regulating gene expression via selective mRNA transport
A critical step in the gene expression pathway that is altered in cancer is nuclear export of mRNA. Dr Wickramasinghe has demonstrated that mRNA export is not constitutive, but highly selective and can regulate distinct biological processes through poorly understood mechanisms. This research project aims to dissect the molecular mechanisms of regulating gene expression via selective mRNA transport. The aim is to establish selective mRNA export as a novel area of research in cancer biology and identify new opportunities for the treatment of cancer. Chief Investigator: Dr Vihandha Wickramasinghe.

Investigating a new class of targeted drugs called Smac-mimetics
These drugs are proving extremely effective in promoting the death of cancer cells. Dr Kearney’s research aims to better understand how Smac-mimetics work as a cancer therapeutic and how they promote immune responses to cancer. This will enable the team to identify combination therapies that elicit both death of the cancer cell and stimulate the immune system to promote tumour clearance.

Chief Investigator: Dr Conor Kearney - NHMRC Early Career Fellowship

WOMEN’S CANCERS
 

STICs and STONes: A Randomised, Phase II, Double-Blind, Placebo-Controlled Trial of Aspirin in Chemoprevention of Ovarian Cancer in Women with BRCA1 and BRCA2 Mutations
Women with an inherited BRCA1 or BRCA2 gene abnormality have a high risk of ovarian and fallopian tube cancers. Removal of the ovaries and tubes can prevent these cancers, but many women delay this preventive surgery until they are post-menopausal. There is increasing interest in the potential of aspirin as a cancer prevention medication. This study, conducted in Australia by the Australia New Zealand Gynaecologic Oncology Group, will determine if daily aspirin could be used as an interim measure to reduce risk of ovarian and fallopian tube cancers before preventive surgery is undertaken. Participants will be assigned to daily aspirin or placebo for 6 to 24 months before their preventive surgery and the incidence of pre-cancers found at the time of preventive surgery will be compared between the two groups. The study will help us better understand how these cancers start and whether aspirin might help prevent them.

Chief Investigator: Prof Kelly-Anne Phillips

Targeting the Oncoprotein MDMX as a Novel Treatment for Triple Negative Breast Cancer
Breast cancer (BrCa) is a leading cause of cancer death in women worldwide. BrCa that does not respond to current therapies has the worst outcomes. This research will investigate a novel strategy to treat these cancers, based on the researcher’s new findings. Two protein targets are: (1) MDMX, found to drive BrCa with its partner, (2) mutant p53, which causes cancer to spread. This research plans to directly target these drivers of aggressive BrCa, using new drugs that individually show great promise in trials in a number of cancers.

Chief Investigator: Prof Ygal Haupt

Combining PI3K, CDK4/6 pathway inhibitors and immunotherapies in triple-negative breast cancer (TNBC): a novel therapy combination
Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancer subtypes, classically affecting young women and characterized by a lack of effective therapies. Assoc Prof Loi’s research shows that blocking both the PI3K and CDK4/6 pathways together effectively reduces TNBC growth in mice and can enhance anti-tumour immune responses. We aim to understand how these drugs work together and if adding immunotherapy can improve responses. Our project could provide a new treatment approach for TNBC patients. Chief Investigator: Assoc Prof Sherene Loi

Molecular profiling residual disease from early stage HER2 positive breast cancer treated with neoadjuvant chemo- and anti-HER2 therapy
Chemotherapy given prior to surgery can provide vital information as to whether a breast tumour is sensitive or resistant to therapy, by the amount of disease remaining at time of surgery. Assoc Prof Loi’s research has further shown the immune response is also important in these patients. Through this research, the Peter Mac team will analyse the tumour samples that remain after chemotherapy in order to understand possible resistance mechanisms as well as how the immunity influences survival of HER2-positive breast cancer patients.

Chief Investigator: Assoc Prof Sherene Loi

Understanding and targeting acquired chemo-resistance in high-grade serous ovarian cancer
Peter Mac researchers have recently discovered a mutation in recurrent high-grade serous ovarian cancer that causes profound overexpression of the multidrug resistance pump, MDR1 (Patch et al Nature 2015). Dr Christie’s research will explore approaches to reverse drug resistance caused by this mutation in recurrent ovarian cancer with a view to using alternative treatments to improve patient outcomes.

Chief Investigator: Dr Elizabeth Christie - New Investigator

Population based genetic testing for high-risk breast and ovarian cancer predisposition genes
Inherited mutations in BRCA1 and BRCA2 confer a very high risk of breast and ovarian cancer. Importantly, once carriers are identified, effective strategies are available that can dramatically reduce the risk of cancer. Professor Campbell’s team will perform genetic testing of a healthy western population to identify breast/ovarian cancer genes before the women develop cancer. Population-based screening could significantly reduce the incidence of these diseases.
Chief Investigator: Prof Ian Campbell

Professor David Bowtell awarded the NHMRC Senior Principal Research Fellowship
Professor Bowtell is one of the world’s leading ovarian cancer researchers. His work focuses on clinical problems of chemotherapy resistance and the development of new therapeutic approaches. His studies are underpinned by the Australian Ovarian Cancer Study (AOCS), one of the world’s most sophisticated clinical cohort studies of ovarian cancer, with over 3000 Australian women enrolled.

IMMUNOLOGY
 

The biogenesis of cytotoxic granules
Cytotoxic lymphocytes are immune cells responsible for killing infected or cancerous cells. How cytotoxic lymphocytes mature from a naïve inactive to a fully activated state as they encounter infected or malignant cells is poorly understood, and will be investigated in the current
proposal. Our results will aid in the development of novel therapies for cancer and other immunological diseases.

Chief Investigator: Dr Ilia Voskoboinik

Targeting adenosine mediated immunosuppression to enhance CAR T cell activity
The use of white blood cells genetically engineered to specifically eradicate cancer cells has been a major recent breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers, due to the immune suppressing nature of the cancer environment. The research will investigate strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.

Chief Investigator: Dr Paul Beavis - New Investigator

Exploiting and defining the immune regulatory activities of BET bromodomain inhibitors
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumour responses. Peter Mac researchers have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. This research aims to define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumours.
Chief Investigator: Prof Ricky Johnstone

BLOOD CANCER
 

Targeting epigenetic enzymes in core binding factor AML
Acute myeloid leukaemia (AML) is a devastating disease and there are ~900 new cases diagnosed annually in Australia. A subset of AML, called core binding factor (CBF) AML is more responsive to conventional chemotherapies than other AMLs however patients still relapse, indicating a need for new therapies. We will use preclinical models of CBF AML to identify the proteins and pathways that these leukaemias are “addicted” to in order to develop new treatment options for these patients.

Chief Investigator: Prof Ricky Johnstone

Clonal Evolution in Myelodysplasia and Acute Myeloid Leukaemia following Azacitidine
The myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) represent a spectrum of clinically heterogeneous malignancies that remain incurable in the vast majority of patients. Whilst the DNA mutations underpinning the initiation/maintenance of these malignancies are largely known, we have little insight into how these mutations alter in response to therapy. Using a range of sophisticated cutting edge technologies we will study how these DNA mutations evolve over the course of treatment.

Chief Investigator: Prof Mark Dawson

LUNG CANCER
 

Enhancing the anti-cancer immune response by combining radiotherapy with immunotherapy
Lung cancer still remains the biggest cause of cancer death in Australia. Recently, immune therapies have shown considerable promise by unlocking the body’s own defences to fight against lung cancer. Dr Siva’s research aims to maximise the effect of anti-PD-1 immune therapy by ‘kick-starting’ the immune response with high-precision stereotactic ablative body radiotherapy (SABR). By completing clinical trials and biological research into the combination of therapies, this research aims to improve outcomes for patients with lung cancer.

Chief Investigator: Dr Shankar Siva - NHMRC Early Career Fellowship

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