Tumour Biology and Targeting

Contact: Prof Maria Kavallairs, m.kavallaris@ccia.unsw.edu.au

Our laboratory leads international research in understanding how the 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, by which time it is extremely difficult to cure. We were the 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 now looking to see which therapies could target this genetic alteration.

Contact: Prof Maria Kavallaris, m.kavallaris@ccia.unsw.edu.au

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, children being treated can experience severe side effects, and survivors can suffer 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 with Team Leader, A/Prof Josh McCarroll, 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.

Identifying the right treatment for the right patient remains a major clinical challenge. So why is this important? Current treatments have been developed empirically through clinical trials. While many children benefit from this approach, approximately 30% fail their treatment, and these children have a high likelihood of dying from their disease.  In collaboration with the Zero Childhood Cancer Program, we are developing avatar models of patient tumours being grown in the laboratory to identify the best treatment for patients. Along with our collaborators, we have pioneered the development of a 3D-bioprinter that can print mini-tumours in a dish in a high-throughput format, so that large numbers of drugs can be screened simultaneously to identify the most effective treatment for individual patients.