In collaboration with radiation oncologists Associate Professor Tom Eade and Dr Eric Hau, principal physicist Professor Dale Bailey, medical physicist Dr Jeremy Booth and others, our radiation research is aimed at improving the diagnosis, treatment and prognosis of cancer using external beam (X-ray) and internal radiotherapy (radionuclides).
63,500 courses of radiotherapy were delivered in Australia in 2016-17
50% cancer patients require at least one course of radiotherapy
50% patients receive radiotherapy within 9 days of diagnosis
Radiation Research Group Leader: Dr Kelly McKelvey
Dr McKelvey is a Post-doctoral Research Fellow whose research achievements have been recognised by a The Brain Cancer Group and Sydney Vital Inflammation Flagship Fellowship and subsequently the inaugural Matt Callander ‘Beanie for Brain Cancer’ HMRI Research Fellowship funded by the Mark Hughes Foundation. Her expertise is in preclinical models of cancer, principally brain cancer, with a major focus of her research being the immune response to multi-modal therapies, including radiation, chemotherapy, immunotherapy, and nanomedicine to increase treatment efficacy and improve patient survival. Her work is contributing to the growing field of research into the role of the immune system in tumour growth and recurrence, and the synergistic effects of combining standard radiotherapy with other therapies to refocus the immune system to combat cancer.
Projects
1. Unravelling the tumour microenvironment to combat brain cancer
Dr Kelly McKelvey, Dr James Wilmott, Dr Connie Diakos, Prof Helen Wheeler, A/Prof Viive Howell
Brain cancers (gliomas) are among the most debilitating and lethal of human cancers, with limited treatment options available. Currently, gliomas are treated with multi-modality therapies (surgery, radiotherapy, chemotherapy, targeted-therapy, and experimental immunotherapy), which can interact in both positive and negative ways to control tumour growth. The development and success of robust new therapies for glioma can only occur by considering and understanding the unique microenvironment in which these tumours develop (i.e. the blood brain barrier and CNS immunity), and the potential impact the different therapeutic interventions have, alone or in combination, on both the tumour and surrounding CNS.
This work utilises preclinical models of brain cancer and the only Small Animal Radiation Research Platform (SARRP; Xstrahl, USA) on the east coast of Australia.
Funding: Sydney Neuro-Oncology Group; Sydney Vital Translational Research Centre; Matt Callander Beanie for Brain Cancer (Mark Hughes Foundation) Hunter Medical Research Institute Fellowship.
2. A new class of theranostics for malignant brain cancer
Dr Hilary Byrne, Dr Kelly McKelvey, A/Prof Viive Howell, Prof Zdenka Kuncic, Prof Louis Redina
Malignant brain tumours including glioblastoma (GBM) are some of the most intractable and aggressive cancers, with a very poor prognosis and low 5-year survival rate. This project aims to assess a completely new class of gadolinium theranostics in preclinical models. Our innovative agents possess a tremendous capacity to target and aggregate within human glioma cell mitochondria in a tumour-selective manner. The expected outcomes of this research will confirm the in vivo potential of this class of theranostics as brain tumour-selective imaging agents for MRI and as radiosensitisers for X-ray irradiation, the first mitochondrial-targeted theranostic platform specifically designed for potential application as dual MRI contrast agents and X-ray radiosensitisers.
Funding: Drug Discovery Initiative Grant
3. Radiosensitisation of high-grade gliomas by modulating glucose metabolism
Dr Han Shen, Dr Kelly McKelvey, Dr Eric Hau
High-grade gliomas (HGGs) comprising glioblastomas (GBM) in adults and diffuse intrinsic pontine glioma (DIPG) in children are a devastating group of cancers, representing the leading cause of brain tumour-related death. Despite advancements in multimodality treatment survival rates continue to be dismal. For decades, radiation therapy (RT) has been the cornerstone of treatment in GBM. This study uses preclinical models of GBM and DIPG to investigate the efficacy of inhibiting glucose metabolism in combination with RT and examine the mechanism of acquired resistance.
Funding: NHMRC
4. New Horizons: Therapeutic applications for medicinal cannabis in the treatment of brain cancer
Dr Matt Dunn, Dr Kelly McKelvey, Dr Adjanie Patabendige, Dr Ameha Woldu, Dr Mengna Chi, Dr Craig Gedye
Brain cancer, in particular high-grade gliomas (HGG), are the leading cause of cancer death in children and adolescents and account for 60-70% of all primary brain and central nervous system cancers in adults. Patients diagnosis with a HGG face a dismal prognosis with an estimated 5-year overall survival rate of 2-3%. In partnership with the Australian Natural Therapeutic Group (ANTG) this project will determine anti-brain cancer efficacy of cannabis in combination with established treatments, namely radiotherapy.
Funding: HMRI Cancer and Medicinal Cannabis Research Project Grant
5. Laying the foundation for improved monitoring and treatment for IDH-mutated gliomas
Angela Cho, Dr Amanda Hudson, A/Prof Viive Howell, Prof Helen Wheeler
The aim of this project is to determine whether radiation resistance in human glioma cell lines is associated with high CA9 levels and whether inhibition or knockdown of CA9 can resensitise glioma cells to radiation. If sensitivity to radiotherapy is enhanced or resensitisation is observed, CA9 may be a potential therapeutic target for glioblastoma.
Funding: Mark Hughes Foundation
6. Exploring a novel nanotechnology strategy for the neo-adjuvant treatment of colorectal cancer by photodynamic therapy and ionising radiation
Dr Wei Deng, Dr Kelly McKelvey, A/Prof Viive Howell, A/Prof Ewa Goldys, Prof Alexander Engel
By combining two clinically accepts therapies, photodynamic therapy and ionising radiation we plan to develop a novel treatment strategy for colorectal cancer. This project will produce gold-labelled nanoparticles for enhance photodynamic therapy in deep tissue in a xenograft in vivo model. Once approved for human therapy this may reduce the radiation-induced mortality and/or increase treatment efficacy.
Funding: Ramsay Research and Teaching Award
7. Towards a personalised theranostics platform through an improved understanding of the biological effects of radionuclide therapy
Takanori Hioki, HyunJu Ryu, Dr Kelly McKelvey, Dr Yaser Gholami, Prof Dale Bailey
This research compares the radiobiological effects of lutetium-177 on human prostate cancer cell lines, with the total dose and dose rate of external beam radiotherapy. Through the establishment of a platform for the highest efficacies of using radionuclide therapy on prostate cancer, it aims to build cellular level justification that will change the way treatment planning is personalised for individuals. Specifically, X-ray radiation will be used to irradiate prostate cancer cell lines, to compare DNA damage to that obtained with beta-particle radiation (Lu177).
Funding: Siemens Research Collaboration
8. Cell breakdown products as a 3D biological marker for radiation dosimetry
Sharon Gordon, Dr Kelly McKelvey, Dr Yaser Gholami, Dr Dale Bailey, Dr Will Rae
Current methods of cancer monitoring, such as MRI imaging, suffer from an inability to distinguish the biological response of the tumour to radiotherapy. These pseudo-responses may be incorrectly interpreted as treatment response, progression of disease, or recurrence. Herein we hypothesise that cellular debris for the irradiated tumours cells are detectable in plasma of patients and can be detected and quantified as a biological measure of treatment effect.
