Identification of new drug targets to improve the treatment of high-grade brain tumours

Identification of new drug targets to improve the treatment of high-grade brain tumours

Official Title: Identification of new drug targets to improve the treatment of high-grade brain tumours

Lead Researcher: Dr Spencer Collis
Non-Clinical PhD Student: Natasha Carmell

Where: University of Sheffield
When: 2015-2018
Cost: £19,700
Research Type: Adult, High-Grade

Natasha Carmell

Identification of new drug targets to improve the treatment of high-grade brain tumours

    Current position:
    Application Scientist at Indica Laboratories – provides technical and 
    application support to academic institutions and large pharmaceutical     
    companies to help in the generation and analysis of medical and 
    scientific research imaging. This is helping in the development and 
    refinement of biomarkers for several human diseases including cancer.

Patient survival rates associated with high-grade brain tumours (the most common form of brain cancer arising in the brain) have improved little over the last 40 years, highlighting an urgent unmet need for more effective treatments for these cancers.
The current standard treatment of these cancers is the surgical removal of as much of the tumour as possible, followed by a course of chemotherapy and radiotherapy. The main chemotherapeutic drug used is called Temozolomide, which is taken as a tablet.
In our cells are a group of over 700 proteins called kinases, which are enzymes that carry out a large amount of the important biological functions within our bodies. As such, the activity of some of these proteins is very often changed in cancers because it helps the cancers to grow fast and become resistant to some of the therapies used to treat them. Because of this, many companies are making drugs towards these enzyme proteins that will hopefully be developed further in new anti-cancer therapeutics.
As part of her PhD studies, Natasha therefore “switched off” each of these 700+ proteins in brain tumour cells to see if this could be a way to make the cancer cells more sensitive to the Temozolomide drug that brain tumour patients take after their surgery. From this work she identified several of these kinase proteins that were making the brain cancer cells resistant to the Temozolomide drug.
Through a large amount of subsequent work, Natasha was able to uncover a new biological understanding as to how one of these kinase proteins in particular can make brain tumour cells resistant to the current Temozolomide and radiotherapy treatments. Importantly, this kinase protein that Natasha identified has been shown to help some other cancers grow and develop. As such, several companies are currently developing new drugs towards it.
We are therefore hopeful that the research carried out by Natasha, generously supported by YBTC, might pave the way for future drug trials that aim to improve the effectiveness of our current treatments for high-grade brain tumours, and give patients and their families some much needed improvements in survival rates.

Work from Natasha's PhD, supported by YBTC, was publsihed on 24th February 2021. CLICK HERE to read it.

Additional Information

See more information about Dr Spencer Collis HERE

See more information about Natasha Carmell HERE

Novel drug targets to augment temozolomide sensitivity in high-grade brain tumours paper HERE
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