Discovery and development of targeted therapies for paediatric brain cancer

Professor Bryan Day
(QIMR Berghofer Medical Research Institute).

Medulloblastoma is the most common type of cancerous brain tumour in children.

Chemotherapy and radiation are the mainstays of current treatment options for children with medulloblastoma. But they generally attack all types of cells in a child’s brain, including healthy ones, and leave the child with long-term neuro-developmental deficits.

The discovery of treatments that specifically target brain cancer cells without harming normal cells is therefore critical to increasing survival and improving long-term outcomes for children with brain cancer.

As part of the Centre for Child and Adolescent Brain Cancer Research, Professor Bryan Day will conduct two innovative research projects to contribute to the discovery of new targeted therapies.

EphA3 a Valid Tumour Specific Therapeutic Target for paediatric Brain Cancer
Professor Bryan Day’s previous research has demonstrated that a specific type of molecule known as an Eph receptor or “EphA3” is only located on tumour cells and is present in approximately 50% of all medulloblastomas. This represents a valuable opportunity to create new treatments known as Antibody Drug Conjugates that specifically attach to EphA3 to deliver drugs that kill brain cancer cells without harming healthy cells.

Using samples obtained from the Queensland Children’s Tumour Bank, Prof Day will expand upon his research to understand the function of EphA3 in multiple types of childhood brain cancer. His innovative research program will also test whether a novel EphA3 Antibody Drug Conjugate can effectively and specifically kill medulloblastoma cancer cells when used alone or in combination with existing chemotherapy and radiation treatments.

Assessment of the Novel OLIG2 Inhibitor CT179 as an Effective Therapy for Paediatric Medulloblastoma Research has shown that 75% of medulloblastoma tumours contain a molecule known as oligodendrocyte transcription factor (OLIG2). OLIG2 is well-recognised for its significance in cancer and is thought to have a functional role in tumour formation in paediatric medulloblastoma. Inhibiting – or blocking – the function of OLIG2 with a therapeutic agent known as CT179 may therefore be an effective way of specifically killing brain tumours.

Professor Day’s prior research has demonstrated that CT179 blocks the growth of medulloblastoma in a laboratory setting. In this new research project, Professor Day will conduct novel experiments to better understand the function of OLIG2 in paediatric medulloblastoma and determine the efficacy of CT179 on inhibiting the growth of paediatric medulloblastoma in preclinical models.

Professor Bryan Day’s research will test whether two novel targeted brain cancer treatments are effective in killing medulloblastoma cancer cells when used alone and in combination with existing standard treatments. The results of this research may be used to inform new clinical trials for paediatric brain cancer patients.

Professor Bryan Day – QIMR Berghofer Medical Research Institute, CCABCR Program, Director Scientific lead of this project

Dr Timothy Hassall – Queensland Children’s Hospital, University of Queensland, CCABCR Program Director Clinical lead of this project

Professor Brandon Wainwright – University of Queensland – IMB, CCABCR Program Director

Professor Greig de Zubicaray – Queensland University of Technology, CCABCR Program Director

A/Professor Kristofer Thurecht – University of Queensland, CAI, Associate – drug development

Emeritus Professor Andrew Boyd – University of Queensland & QIMR Berghofer Medical Research Institute, Associate – intellectual/clinical support

• Professor Terrance Johns – Telethon Kids Institute, Associate – intellectual/model support