COMPLETED PROJECT OVERVIEW

Plymouth University - Professor Oliver Hanemann

This research on schwannomas and meningiomas used a unique human cell culture model using cells derived from surgical patients. This has led to the identification and testing of new, targeted therapies and the team have successfully translated their research into early clinical trials. This approach has allowed them to screen approved drugs directly and go straight into clinical trials, avoiding pre-clinical animal trials.

PROJECT OUTCOMES

Meningiomas and schwannomas are primary brain tumours affecting brain and spinal cord. Meningiomas in particular are amongst the most common brain tumours. They are usually not aggressive; however, when becoming symptomatic the only available treatment is surgical resection or radiotherapy, which can leave patients with mild to severe morbidity. Meningiomas and schwannomas can grow simultaneously in patients affected by the genetic condition Neurofibromatosis type 2, which predispose them to a continuous recurrence of these tumours. No pharmaceutical treatment is available to treat these patients, so new therapeutic strategies are urgently needed.

The aim of this project was the identification of novel specific and/or common therapeutic targets in meningiomas and schwannomas by using a proteomic approach.

It is well known that tumours originate because the accumulation of several mutations that occurs on the control centre of our cells, the DNA. The DNA codifies all the information in the body; the colour of the eyes, the shape of the nails, the tone of the skin, etc. and most importantly it defines the behaviour of the different cells in the different compartments of our body. When this information is not produced correctly the cell becomes ‘confused’ and, when the cell is able to survive to this ‘confused state’, it starts to grow without control thus generating a tumour mass.

In decades of research scientists have been able to characterized most of the mutations that affect the DNA and that are responsible for the tumour growth. This has been very well studied also in meningiomas and schwannomas, but, despite we know the reasons why these tumours are growing, this information is not sufficient to find an effective therapy.

Indeed, the drugs commonly used in chemotherapy are not capable of attaching the DNA at the specific injured sites that cause the cell to be ‘confused’ but they attack the proteins.

Proteins are the effectors of the information codified by the DNA, they are the cellular workers that obey to the orders given by the DNA, and most importantly they are drugable.

Cancer therapy is moving towards a more selective and efficient approach that is defined ‘molecular targeted therapy’. Tumour cells differ from heathy cells in the content of proteins, in particular, some proteins can be highly present in the tumour cells but barely present in heathy cells and this feature confers the protein the title of ‘therapeutic target’. A drug capable of specifically target a protein localised mainly on tumour cells it would be highly specific and effective against the tumour, at the same time preserving the healthy tissue from the side effects of the drug.

In this context we analysed the protein content of schwannomas and meningiomas and compared it to the healthy cells where the tumour originates from. We identified hundreds of differences, thus defining the signature of these tumours. Some proteins were highly present only in one tumour type but not in the other; however, few proteins where found in both tumour types but much less in the healthy cells.

We confirmed that the targets we are currently working on are responsible for an increased cellular proliferation, meaning that therapeutically targeting these proteins can control tumour growth and possibly reduce the tumour mass.

We are currently looking at drugs, already available in clinical practice or trials, which can specifically target our proteins of interest. The use of drugs that have been already approved is time and cost effective and will allow us to move quicker to clinical trials. Importantly, we won’t need to perform any drug testing on animals to examine the safety of the drug.

Our research approach allowed us to predict novel therapeutic targets and also biomarkers using the surplus tissue after surgical resection of the tumour, without any need to recreate the tumour in mice, thus saving hundreds of animals, and at the same time gaining more reliable results.

We are extremely grateful for the financial support received from AFR UK and its supporters which made this research possible. One step forward in the fight against these tumours has been made and we won’t stop until we will find a cure, this is our promise to the patients and the supporters who believed in us.