Whilst current therapies have become more effective at killing cancer cells, 70% of childhood cancer patients will experience side effects. Around 30% of survivors will have serious, chronic side-effects as adults, such as heart conditions, infertility, metabolic disorders or secondary cancers – all caused by the cancer treatment that saved their life.
In most cases, toxic drugs that flood the entire body are a treating clinician’s only option. If we can better understand the specific molecular causes of cancer in a child, we can target these with more effective treatments to increase survival rates and improve long term quality of life.
Our research objectives are to:
- investigate how cancer cells grow and survive
- identify therapeutic targets for childhood cancers
- develop nanomedicine drug delivery for cancer
- investigate nano-based diagnostics and personalised medicine for childhood cancer
- develop 3-dimensional multicellular models of childhood cancer for therapeutics and cancer biology
Our funding includes grants from the National Health and Medical Research Council (NHMRC), Australian Research Council (ARC), Tour de Cure and Cancer Institute NSW.
Professor Maria Kavallaris
Our laboratory leads international research in understanding how the skeleton (cytoskeleton) of cancer cells can cause cancer drug resistance. We identified microtubule proteins in the cytoskeleton that can make tumour cells resistant to specific chemotherapy drugs. We can make tumour cells more sensitive to chemotherapy when we ‘silence’ specific cytoskeletal genes using gene silencing tools and are identifying genes regulated by cytoskeletal proteins to explore future therapeutic targets.
The childhood cancer neuroblastoma is often diagnosed as advanced stage (metastatic) disease, when it is extremely difficult to cure. We were first to discover that a protein called stathmin helps neuroblastoma cells to metastasise. We investigated the genetic signals responsible to better understand the biology of the disease and develop new therapeutic approaches. We found a specific genetic change that drives the cancer cells’ spread and is found in aggressive neuroblastoma. We are looking to see which therapies could target this genetic alteration.
Professor Maria Kavallaris
Dr Joshua McCarroll
Dr Orazio Vittorio
Current treatment protocols for childhood cancer involve chemotherapy agents that are highly toxic and designed to kill all rapidly dividing cells in the body, including normal healthy cells. As a result, patients can experience severe side effects, and for survivors, lifelong health issues.
Nanomedicine is a new approach that involves designing biodegradable polymers, tiny molecules composed of repeating structural units, that can package and deliver therapeutic drugs or genetic material specifically to tumour cells while avoiding normal healthy cells. We work with research chemists at the Australian Centre for NanoMedicine and international collaborators to develop nanomedicines for difficult-to-treat and aggressive cancers. We are developing and evaluating nanoparticles that can deliver either gene-silencing material or chemotherapy to tumour cells.
Our laboratory studies show that our ‘Star nanoparticles’ can deliver gene silencing material to a number of cancer types to silence gene expression that drives cancer growth. When these genes are switched off using our Star nanoparticle delivery system, the cancer cells stop growing and die. We are extending these studies to several aggressive childhood cancers.
Neuroblastoma, brain cancer and a range of other tumours need high levels of copper to grow. We developed a nano-formulation of a natural product called catechin, found in green tea, known to have anticancer properties. Our nano-formulation dextran-catechin can disrupt copper balance inside cells and block tumour cell growth by inhibiting the formation of tumour blood vessels that fuel tumour growth and spread. We’re extending this work to an incurable childhood brain cancer called glioblastoma.
In collaboration with research chemists and radiobiologists at the Australian Nuclear Science and Technology Organisation (ANSTO), we are also developing techniques for imaging cancer cells using their high levels of copper and showing we can deplete copper in tumours in mice with our nano dextran-catechin formulation.
Professor Maria Kavallaris
Solid tumours such as neuroblastoma and brain cancer grow in a complex tumour microenvironment that influences how tumour growth and response to cancer therapies. The standard way of growing and testing cancer cells in two-dimensions (2D) on a plastic dish does not accurately reflect tumour complexity or at times, response to therapy. Three-dimensional (3D) tumour spheroids better mimic the 3D tumour environment.
As part of the Zero Childhood Cancer national personalised medicine program, led by Children’s Cancer Institute and the Sydney Children’s Hospitals Network, we are developing avatar models of patient tumour samples grown in the laboratory to identify the best treatment for individual patients. We have successfully developed 3D tumour models from these which will allow us to further understand the factors that influence how a tumour will respond to potential treatments. In an exciting advance, we are collaborating with research chemists and an industry partner to develop a high-throughput device to bioprint tumour cells as spheroids and tumour organoids. This will allow detailed analysis of tumour biology and drug screening in the future. The ultimate aim is to develop these models for patient tumour testing in our ACRF Drug Discovery Centre.
Group LeaderProfessor Maria Kavallaris
SCIENTIA RESEARCH FELLOW
Dr Angelica Merlot
Dr Lakmali Atapattu
Dr Simon Brayford
Dr Marion Le Grand
Dr Friederike Mansfeld
Dr Laura McVeigh
Dr Ernesto Moles
Dr MoonSun Jung
Dr Walter Muskovic
Dr Shehzahdi Moonshi
SENIOR RESEARCH ASSISTANT
Dr David Chang
Zerong (Shirley) Ma