Molecular profiling of tumours helps guide treatment and inform prognosis. In some cancers, this profiling can be carried out non-invasively via blood tests that detect genetic material that is shed from the tumour. Brain tumours do not shed this material into the blood in the same way, however.
Professor Hamerlik and colleagues are developing an innovative device that will use tear fluid to detect the presence of a substance produced by cells in some types of brain tumour. By enabling a more precise diagnosis at an earlier stage, this could drive the development of personalised treatment.
Low-grade gliomas are slow-growing but incurable brain tumours that predominantly affect teenagers and young adults. Current treatment consists of 'debulking' surgery, followed by radiotherapy and a prolonged surveillance period using MRI. All patients ultimately progress to high-grade glioma, at which point their prognosis is around two years.
Some types of low-grade glioma have mutations in a gene called IDH. These mutations are important in terms of clinical management of the disease as they may predict response to treatment; being able to confirm their presence at an early stage could help doctors to select the best treatment approach.
The IDH mutations can be detected using techniques that analyse tumour tissue that has been removed via biopsy or surgical resection, but this can cause delays in treatment planning. They can also be detected in the cerebrospinal fluid, the fluid that surrounds and protects the brain and spinal cord, but collecting this fluid is an invasive and risky procedure.
Progress has been made with the development of blood tests that can identify so-called biomarkers for cancers such as breast, prostate and lung, but these blood tests don't work well for brain cancer. This is because the unique environment inside the brain prevents cancer 'material' (cells or parts) being released into the blood.
As an alternative and novel approach, Professor Hamerlik proposes that tear fluid could be used for detection and monitoring of biomarkers for low-grade glioma.
In this project, the team will develop and test a biosensor device that will enable them to detect a substance called D-2HG in tears. D-2HG is uniquely produced by cells in tumours that carry the IDH mutation.
Their work is based on strong preliminary data demonstrating feasibility of the approach.
A non-invasive, simple diagnostic tool like this biosensor device could bridge the gap between invasiveness and precision.
By enabling a more precise diagnosis at an earlier stage, it could provide a better, earlier understanding of prognosis and optimal therapy, enabling better stratification in clinical trials, and driving the development of personalised treatment.
This proposal brings together a strong, multi-disciplinary team with extensive expertise in neuroscience, oncology, electrochemistry, bioengineering and in vivo research. They are uniquely placed to deliver this project.
Professor Petra Hamerlik is a world-leading researcher in translational neuro-oncology and has pioneered the development of the study from its inception in Denmark.
She is working with University of Manchester colleagues Professor Marloes Peeters, Chair of Engineering Biology, and Professor Alex Casson, Professor Biomedical Engineering. External clinical collaborators Dr David Coope and Professor Maria Castro ensure that there is a clear line of sight from the laboratory to the clinic.
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