Understanding the molecular mechanisms which drive brain cancer recurrence and defining novel therapies to target these aggressive tumour cell populations

Glioblastoma (GBM) is the most common and aggressive adult primary brain cancer. Median survival is <15 months and only about 10% of patients survive two years without disease recurrence. Therefore, there is a critical need to search for new and innovative approaches to patient management and treatment. It is well understood that GBM cells are adaptive to chemotherapy and radiation treatment which is the cause for tumour recurrence and subsequent death. The mechanisms that lead to this recurrence are poorly understood.

As part of the QIMR-Berghofer Brain Cancer Tissue Bank, we have collected a series of patient specimens which include primary tumours that have not undergone treatment and matching post-treatment recurrent tumours. This is a valuable and rare resource. We are utilising these pair-matched specimens and cell cultures to elucidate how malignant brain tumours develop resistance. By understanding the molecular functions that cause treatment resistance, we will be able to design therapies to prevent recurrence and improve patient outcomes.

The aim of this project will be to understand how these aggressive tumours reform following therapy by undertaking an in-depth analysis of pre- and post-treatment paired GBM specimens. We believe that to significantly improve outcomes for patients with GBM we first need to understand in detail how tumour cells can survive standard therapies and recur. Once differences between multiple primary and recurrent GBM specimens have been identified, the project will aim to validate candidate therapeutic targets in preclinical animal models. Outcomes from this project will include the definition of novel molecular mechanism’s associated with recurrence and potentially define novel therapies suitable for testing in clinical trial. Ultimately these therapies could prolong the life of sufferers of these incurable diseases.

For more information on this research group: http://www.qimrberghofer.edu.au/lab/sid-faithfull-brain-cancer-laboratory/