Investigators: Raelene Endersby, Nick Gottardo, Jacqueline Whitehouse, Meegan Howlett, Jessica Buck, Mathew Ancliffe, Jessica Lawler, Kale Somers, Hilary Hii, Brooke Carline, Mani Kuchibhotla, Kale Somers
Project description
Brain tumours are the major cause of childhood cancer deaths. This project focuses on the most common malignant brain cancer of childhood - medulloblastoma. Survival rates for these patients have not significantly improved in recent decades and more effective therapies are needed. Our goal is to identify the best novel drugs to take forward into new clinical trials for medulloblastoma. To achieve this, we screened drug libraries for agents that effectively inhibit medulloblastoma cell growth and identified several kinase inhibitors that block the ability of cancer cells to repair the DNA damage caused by conventional therapy.
This project is focused on several kinase inhibitors which target cell cycle control and the DNA damage response pathway. Radiation therapy causes DNA damage, and we hypothesise these kinase inhibitors will enhance the effects of radiation therapy. This will be investigated using a new resource – the X-RAD SmART – the first machine in Australia that can precisely mimic clinical radiation therapy in pre-clinical models.
Previously, we determined that prexasertib has chemo- and radiosensitising effects in medulloblastoma. This project expands this work to compare the efficacy of mutliple different drugs and determine which is the most effective. Our research utilises sophisticated models of medulloblastoma and innovative new equipment to obtain clinically relevant data. The work investigates the mode of action for these drugs in cancer, as well as in normal brain to identify potential side effects of treatment.
Our results will determine how to effectively incorporate the new drugs into existing treatment protocols and provide the evidence needed to justify a new children’s brain cancer clinical trial.
Collaborators
- Martine Roussel
- Brandon Wainwright
- Laura Genovesi
- Martin Ebert
Partners
- National Health and Medical Research Council
- Cancer Australia
- The Kids Cancer Project
- Pirate Ship Foundation
- Ethan Davies Foundation