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Project Title: Targeting the epidermal growth factor receptor in high grade glioma

Grant Amount: $200,000

Institution: Hudson Institute of Medical Research

Investigator Team: Principal investigator Prof Terry Johns 

Grant Type: 2014 Innovation Grant

Years: 2014 - 2016

High-grade glioma (HGG) is among the most lethal and difficult to treat of all cancers. 

Recent advances in cell culture methodology now allow us to grow HGG cells directly from patients and retain the features of the original tumour, both in vitro and as tumour xenografts. Cell lines generated by this technique provide an exceptional platform for discovering new, innovative therapeutic approaches. 

Prof Johns will utilise a unique collection of HGG cell lines and xenograft models to determine the mechanisms controlling the response to a group of therapeutics that target the epidermal growth factor receptor (EGFR). . 

Highlighted Quote: “Recent advances in cell culture methodology now allow us to grow HGG cells directly from patients and retain the features of the original tumour... Cell lines generated by this technique provide an exceptional platform for discovering new, innovative therapeutic approaches.” - Prof Terry Johns

Progress: 

The main problem with approaches that use drugs that specifically target receptors like EGFR is the development of resistance (i.e. the drugs stop working). Resistance can be de novo (i.e. the brain cancer is resistant from the start) or acquired (i.e. the brain cancer initially responds to the treatment but then becomes resistant). During the 2 years of this grant, we have used our unique panel of patient-derived brain cancer cell lines to address both forms of resistance. 

We have successfully identified both de novo and acquired mechanisms that cause resistance to drugs targeting these receptors. This is important as, eventually, if we successfully move these agents into the clinic, we will need to know which patients to select to avoid unnecessary treatment of patients who will not respond. 

With respect to de novo resistance, we have developed several new strategies for overcoming resistance to EGFR-targeted drugs in brain cancer. We are continuing to work on strategies for moving these towards the clinic. 

Preventing or overcoming acquired resistance is one of the most important challenges in cancer, including brain cancer. As part of this grant, we have developed patient-derived brain cancer cell lines that have acquired resistance to EGFR drugs. We have commenced analysing the mechanisms that cause this resistance. This is a very valuable resource and has only been made possible through CBCF support, as the development of such valuable tools is difficult to fund through government grants.

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