Discovery and development of targeted therapies for paediatric brain cancer

Professor Bryan Day
(QIMR Berghofer Medical Research Institute).

Professor Bryan Day's research falls under two innovative projects to contribute to the discovery of new targeted therapies. The first project will build upon Professor Bryan Day’s previous research, which has demonstrated that a specific type of molecule known as “EphA3” is only located on tumour cells and is present in approximately 50% of all medulloblastomas. This presents a valuable opportunity to create new and specifically targetable treatments 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.

The second project involves researching a molecule known as oligodendrocyte transcription factor (OLIG2), which is found in 75% of medulloblastoma tumours. OLIG2 is well-recognised for its significance in cancer and is thought to have a large role tumour formation in paediatric medulloblastoma. Inhibiting the function of OLIG2 with a known therapeutic agent may be an effective way of specifically killing brain tumours.

The 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.

The potential outcomes

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. It is hoped that the results of this research can be used to inform new clinical trials for paediatric brain cancer patients.

The research team

Prof Bryan Day

QIMR Berghofer Medical Research Institute, CBCC Program, Director Scientific lead of this project

Dr Timothy Hassall

Queensland Children’s Hospital, University of Queensland, CBCC Program Director, Lead Clinical Investigator

Prof Brandon Wainwright

University of Queensland – IMB, CBCC Program Director, Lead Scientist Investigator

Prof Greig de Zubicaray

Queensland University of Technology, CBCC Program Director

A/Prof Kristofer Thurecht

University of Queensland, CAI, Associate – drug development

Emeritus Andrew Boyd

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

Prof Terrance Johns

Telethon Kids Institute, Associate – intellectual/model support

Profile

https://www.qimrberghofer.edu.au/people/bryan-day/