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The Plymouth team, led by Prof Oliver Hanemann, has a world-leading track record in researching low-grade brain tumours occurring in teenagers and adults. By identifying and understanding the mechanism that makes a cell become cancerous, the team can explore ways to halt or reverse them.
The team is focusing on meningiomas and schwannomas, which are two common brain tumours that form both spontaneously and when associated with an inherited condition -- neurofibromatosis 2. At present, there are no drugs approved to treat either of these types of tumour. Patients have only surgery and radiotherapy as their treatment options and these are not always effective, or even possible, depending on the location of the tumour within the brain.
A key innovation which has been developed within the Centre is a fast track drug screening programme - testing new drugs in human cells grown in the lab. This information will be used for the development of innovative early-stage clinical trials in order to make new drug therapies available to patients both safely and faster.
The researchers have a particular focus on ‘personalised medicine'. Not all patients respond to treatment with existing medications. This is largely due to the massive diversity between tumours, the presence of many cells within a tumour expressing different proteins (that dictate how a person will respond) or how likely their tumour is to become resistant to a particular drug. The research programme aims to identify particular subgroups of patients which will respond to specific treatments which will be more effective.
Using a technique called mass spectrometry, the researchers can analyse brain tumour samples which have been obtained from patients following surgery. They analyse the cellular ‘proteomic signature’, which identifies the proteins that are expressed differently in cancer cells when compared with normal cells. This information to can be used to identify potential target targets which may be responsive to drugs already available.
These can then be tested on tumour cells in the laboratory, as a pre-clinical assessment of their effectiveness, and quickly form the basis of early stage clinical trials.
The researchers can also take brain tumours known to have specific genetic mutations, define their proteomic signatures associated with these mutations and again compare them with those in normal cells. This will allow the researchers, in the longer term, to look directly for specific features in each patient’s tumour that will help them choose the best personalised treatment option.
Their most recent project is looking at patient blood samples to identify biomarkers. These are factors present in the blood which may change in people with specific types of tumour. They can help us to decide on the best course of action based on the fingerprint of the tumour. The advantage of this technique is that it is much less invasive than a tumour biopsy.
Plymouth University’s long-term vision is that they will be able to characterise each tumour into subcategories, giving patients a higher chance of responding to a particular drug. They aim to use this process within the next few years using a modern trial design.
"We will find a drug therapy and, because we work using a fast-track method, we will get it to patients quickly.” – Professor Oliver Hanemann, Associate Dean Research and Research Lead for Brain Tumour, Plymouth University.
Cooper J, Xu Q, Zhou L, Pavlovic M, Ojeda V, Moulick K, de Stanchina E, Poirier JT. Zauderer M, Rudin CM, Karajannis MA, Hanemann CO, Giancotti FG. (2017). Combined inhibition of NEDD8-activating enzyme and mTOR suppresses NF2 loss–driven tumorigenesis. Mol Cancer Ther doi: 10.1158/1535-7163.MCT-16-0821
Bassiri K, Ferluga S, Sharma V, Syed N, Adams CL, Lasonder E, Hanemann CO (2017). Global proteome and phospho-proteome analysis of Merlin-deficient meningioma and schwannoma Identifies PDLIM2 as a Novel Therapeutic Target. EBioMedicine. 2017 Feb;16:76-86.
Zhou L, Lyons-Rimmer J, Ammoun S, Müller J, Lasonder J, Sharma V, Ercolano E, Hilton D, Taiwo I, Barczyk M Hanemann CO (2016) The scaffold protein KSR1, a novel therapeutic target for the treatment of merlin deficient tumours, Oncogene, 35(26):3443-53.
Schulz A, Buettner R, Hagel C, Baader SL, Kluwe L, Salamon J, Mautner VF, Mindos T, Parkinson DB, Gehlhausen JR, Clapp DW, Morrison H (2016) The importance of nerve microenvironment for schwannoma development, Acta Neuropathologica 132,(2), 289–307
Hanemann CO, Blakeley JO, Nunes FP, Robertson K, Stemmer-Rachamimov A, Mautner V, Kurtz A, Ferguson M, Widemann BC, Plotkin SR, Evans DG, Ferner R, Carroll SL, Korf B, Wolkenstein P, Knight P (2016). Current status and recommendations for biomarkers in Neurofibromatosis 1, Neurofibromatosis 2 and schwannomatosis, Neurology, 87(7 Suppl 1):S40-8.
Ammoun S, Schmid MC, Zhou L, Hilton DA, Barczyk M, Hanemann CO (2015). The p53/mouse double minute 2 homolog complex deregulation in merlin-deficient tumours Mol Oncol. 9(1):236-48
Button RW, Lin F, Ercolano E, Vincent JH, Hu B, Hanemann CO, Luo S (2014). Artesunate induces necrotic cell death in schwannoma cells. Cell Death Dis.5:e1466.