Results from the 2019 Research Grant Round

Each year the Cancer Society administers a national grant round to fund cancer research. It is part of the Cancer Society's mission to reduce the incidence and impact of cancer in our communities. A voluntary committee of research experts across Australasia apply a rigorous assessment procedure in order to rank applications.

In 2019, nine multi-year projects out of fifty-two applications were successful in securing funding. Brief summaries of 2019-funded projects follow:

 

A pilot clinical trial of a stoma output recycling device

Associate Professor Gregory O’Grady / University of Auckland

About the project

A temporary ileostomy is used often for people with colorectal cancer. This procedure attaches the opened small intestine onto the skin through an incision in the abdomen. Gut contents then flow into a bag instead of passing through the colon. Aside from posing a challenge to patients, ileostomies cause fluid and nutrient loss due to bypass of the resorptive functions of the bowel. This often leads to dehydration or impaired kidney function, especially in patients undergoing chemotherapy.

This may mean patients with stomas missing doses of chemotherapy, or requiring changes to their treatment. A further 10% of patients are readmitted to hospital for fluid replacement, all due to ‘stoma-diarrhoea’.

This pilot evaluates a new device that prevents nutrient and fluid loss from stomas. It works by simply pumping the effluent from the stoma back into the intestine. Researchers have shown this device works and is safe. They now hope to run a small pilot randomized trial in patients having chemotherapy, to see if the device is practical, effective and well-liked. If successful, researchers will run a larger trial. The device will become important in improving outcomes for cancer patients with stomas.

 

He Tapu Te Whare Tangata: Exploration of the cervical screening clinical pathway

Ms Anna Adcock (Ngāti Mutunga) and Dr Kendall Stevenson (Ngāti Awa, Ngāti Kurī, Ngāpuhi) / Victoria University of Wellington

About the project

New Zealand’s National Cervical Screening Programme (NCSP) has effectively decreased rates of cervical cancer incidence and mortality, but has not provided equal success for Māori. Technological innovation provides an opportunity to address these inequities.

The Human Papilloma Virus (HPV) causes cervical cancer, and the HPV test, which can be self-taken with a vaginal swab, is a more effective screen for preventing cervical cancer than cytology. Through a Ministry of Health grant this research team has shown HPV self-testing is acceptable for Māori women and are now carrying out a successful Health Research Council-funded clinical trial offering the HPV self-test to never/under-screened women in Northland. After 12 months, more than half of the eligible women (in the intervention group) have been screened.

But a knowledge gap has been found about the lived experiences of women when offered the test, when screened, and when journeying to diagnosis/treatment. This project aims to look at these issues and knowledge gaps to inform NCSP policy to address cervical cancer inequities for Māori. The research team argues the entire cervical screening clinical pathway must be culturally responsive and guided by patient experience to be successful.

How will it help people affected by cancer?

This research will fill in knowledge gaps around how HPV self-testing should be implemented in the new NCSP. Potential barriers and facilitators to accessing HPV based screening and specialty/diagnostic services will be explored. Ultimately, this research aims to address cervical cancer inequities for Māori by informing a more culturally responsive and patient led clinical pathway.

 

Inducible safety for anti-cancer T cells

Associate Professor Alexander McLellan / University of Otago

About the project

Cancer treatment has been revolutionised by the development of chimeric antigen receptor (CAR) T cells. CAR T cells attack and kill cancer cells that are recognised by the CAR. Unfortunately, a major side effect of this treatment is a life-threatening cytokine release syndrome (CRS) caused by the release of inflammatory cytokines. Although the mainstay treatment for CRS is glucocorticoids, these can destroy the adoptively transferred T cells, leading to the failure of an expensive and potentially life-saving treatment.

This project will develop a system to change T cell activation and prevent the onset of CRS. The system will use synthetic promoters and a control 'switch' within the CAR T cell to enhance T cell safety. These automated promoter-switches will make cell-therapy much safer for people with cancer.

 

Identifying novel precursor biomarkers of ovarian cancer 

Dr Janet Pitman / Victoria University of Wellington

About the project

Ovarian cancer (OC) is the most lethal gynaecological cancer in New Zealand and world-wide. Despite an improvement in our understanding of OC causes, survival rates have remained consistently low due to the lack of symptoms shown in OC. The lack of ovarian tissue biopsies from symptomless women have hampered research on early stage detection.

Researchers have access to a unique murine knock-out model that spontaneously develops ovarian cancer similar to that of human ovarian cancer. As the ovarian cellular transformations that led to distinct tumour phenotypes are systematic, this model is ideal for providing proof that circulating biomarkers of precursors of OC may be detected. This research will examine the population of coding and non-coding RNAs in mice and humans at the onset of OC. This information will then be used to provide proof that nucleic biomarkers present in the circulatory system can detect early signs of ovarian cancer.

 

Combination of oncolytic virotherapy with chemotherapeutic agents in breast cancer

Dr Laura Burga / University of Otago

About the project

Oncolytic virotherapy is an emerging, promising field in cancer treatment that uses viruses to selectively kill tumours. Seneca Valley Virus (SVV) is an oncolytic virus which targets cells that overexpress a protein called Tumour Endothelial Marker 8 (TEM8). Over 60% of human tumours including an aggressive form called triple negative breast cancers (TNBC) have this protein. Moreover, in TNBC, this protein was linked to tumour growth, migration, metastasis and resistance to therapy. In this project we will investigate the ability of SVV to improve the potency of current chemotherapeutic agents to enhance tumour cell death in tissue cultures and in mouse models of breast cancer. The effect of this combination therapy could improve the effectiveness of the drug, reduce the chemotherapeutic agents’ side-effects and ultimately improve the treatment outcome and patient quality of life.

How will it help people affected by cancer?

This study could identify a new strategy for targeted therapy of aggressive forms of breast cancer. A successful combination therapy will have several advantages to patients: on one hand, the oncolytic virus will target cancer stem cells responsible for relapse and metastasis, on the other hand it will lower the amount of chemotherapeutic drugs thus decreasing the cytotoxicity associated with chemotherapy.

 

Harnessing the gut microbiome to predict response to radiotherapy in rectal cancer

Dr Rachel Purcell / University of Otago

About the project

The over-arching aim of this project is to understand how differences in the microbiome relate to radiotherapy response in the treatment of rectal cancer, and how we can harness this knowledge to develop predictive biomarkers of treatment response.

How will it help people affected by cancer?

Being able to predict response to radiotherapy will identify people who won’t respond well to radiotherapy. This will mean that they could proceed directly for surgery, avoiding treatment delays and the side-effects associated with radiotherapy. It will also identify people who may respond well to radiotherapy and benefit from a “watch and wait” approach, thereby avoiding surgery.

 

Efficacy of a growth hormone receptor antagonist against Melanoma

Dr Joanna Perry / University of Auckland

About the project

This project has in vitro evidence demonstrating that growth hormone (GH) stimulation stimulates signal transduction and promotes proliferation in a panel of primary metastatic melanoma cell lines, and that GH receptor (GHR) blockade prevents this (unpublished data, Cancer Society funded project). Whether GHR blockade inhibits tumour growth has not been determined. The aim of this project is to determine whether the GH signalling plays a role in regulating tumour growth in a more realistic in vivo situation where systemic production of GH and interactions with factors produced in the tumour microenvironment will come into play.

 

Post-doctoral Fellowship: Micro-pharmacokinetic models of tumour radiosensitisation by DNA-PK inhibitor prodrugs

Mrs Cho Hong / University of Auckland

About the project

Radiotherapy plays a central role in the management of cancer. DNA-dependent protein kinase (DNA- PK) exerts a key role in repair of radiation-induced DNA damage and acts as a resistance mechanism to radiotherapy. Therefore, targeted delivery of inhibitors of DNA-PK that can selectively sensitise tumours to radiation can potentially improve clinical outcomes. Existing DNA-PK inhibitors sensitise tumour cells to radiotherapy, but also cause normal tissue toxicity.

Research led by Associate Professor Hay in the lab has recently discovered new, potent and tumour-selective inhibitors of DNA-PK. Critical to the preclinical development of these prodrugs are predictive models of pharmacokinetics (PK) and pharmacodynamics (PD) within tumours. This project will allow Cho Hong to develop PK/PD models that accurately predict anti-tumour activity and to identify the most active prodrugs for preclinical evaluation. The tools Cho will develop in this project will aid in the discovery and development of other new drugs for cancer treatment.

 

PhD Scholarship: Identifying protective T cell functions in the tumours of people with colorectal cancer

Ms Jessica Harte / University of Otago

About the project

The immune response has been shown to be an important factor in determining patient survival in colorectal cancer. However, the immune response within the tumour can consist of cells that both support or inhibit tumour growth. Immune therapies that have been successful in a number or other cancers have not been as successful in treating colorectal cancer. I hypothesise that the tumours of people with colorectal cancer contain unique immune signatures that can be used to predict the outcome of individuals and therefore help to better target therapies. I will study the composition of the immune cells in the tumours of people with colorectal cancer and identify potential targets for improved immune therapy.