Each day, approximately six Australians are diagnosed and four die from primary brain and CNS cancers. They carry the largest lifetime cost (AUD$1.9million) per person of any cancer in Australia. Glioblastoma multiforme (GBM) is the most common and aggressive adult brain cancer where 2-year survival is only 25%. Standard treatment is usually not curative and includes maximal safe surgery followed by adjuvant radiotherapy and chemotherapy. At recurrence, treatment options are limited and there is no standard approach; with temozolomide (TMZ) being the most prescribed treatment. Despite numerous clinical drug trials, no breakthroughs have occurred for nearly 15 years. One important limitation has been the blood-brain barrier (BBB), which prevents drug penetrating the tumour and can lead to intolerable toxicities outside the central nervous system (CNS) where required concentrations are usually higher. A paradigm shift is needed to change the way that preclinical research translates to novel treatment. Nanomedicine is a potential solution, utilising nanoparticles to target the GBM and precisely deliver a therapeutic drug-payload (a nanotherapeutic) that may not have been possible via conventional administration routes.

This project explores an innovative route to establish a GBM nanomedicine-treatment pipeline, progressing our preliminary understanding and recent advances, ultimately translating proof-of-principle outcomes in mice, through to canine patients with this devastating disease and finally to humans with recurrent GBM. This project is a combined collaboration the Brisbane Veterinary Specialist Centre and medical and radiation oncologists from the Princess Alexandra Hospital. It combines the power of these two clinical translation pathways with our expertise in nanomaterial design for drug delivery and custom bespoke bispecific antibody technology established in part by the Thurecht group.