Brain tumours

In France, about 5000 new people with primary malignant brain tumour are diagnosed each year.
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DISEASE DESCRIPTION

Brain tumours can have two origins : so called primitive tumours occur directly in the brain. Metastatic or secondary tumours, on the other hand, develop in the lung, colon, breast or skin, before reaching the brain.

Malignant tumours are tumours growing rapidly, leading to the destruction of the brain area where they have settled, whereas benign « low-grade » tumours evolve more slowly without causing destruction.

The most common primary tumours are gliomas, originating from glial cells (astrocytomas and oligodendrogliomas). Low-grade tumours are mildly aggressive but in most cases they evolve in a more malignant form, called high-grade tumour.

Tumours developing from the meninges called meningiomas are very common and most often benign.

We also find lymphomas from brain immune system cells, ependymomas (tumours stemming from brain ventricle walls). Neurinomas or schwannomas come from Schwann cells (glial cells responsible for the formation of the myelin sheath around the axon). Finally, we also find adenomas, developing from hypophysis.

SYMPTOMS

Symptoms depend on tumour location, size and growth speed. Gliomas account for approximately 50 to 60 % of all primitive malignant tumours. Conversely, meningiomas are common benign tumours.

Currently, brain tumour treatments involve, according to cases, surgery, radiotherapy or chemotherapy, but often do not allow healing.

CAUSES

Today, we partially know the reasons why a cell continues to multiply and becomes a tumour instead of dying, according to  » its lifespan « . A brain tumour can develop from any area of the brain : hemispheres, cerebellum, brainstem, and hypophysis.

PREVALENCE

About 5000 new people with primary malignant brain tumour are diagnosed each year in France.

ICM RESPONSES

TOPICS AND RESEARCH TEAMS

  • Identify causes and understand tumour development mechanisms to highlight potential therapeutic targets with Emmanuelle Huillard’s team.
  • Develop diagnostic and prognostic tools to detect the genetic mutations involved in tumours, analyse their prognostic or predictive value of the response to treatment, and thus provide useful information to clinicians with Marc Sanson’s team.
  • Develop personalised therapies based on each patient’s tumour genetic profile with Marc Sanson’s team.

HIGHLIGHTS

New genes involved in oligodendrogliomas : TCF12

Thanks to an international collaboration and the POLA network coordinated by Pr Jean-Yves Delattre from the ICM, Emmanuelle Huillard and Marc Sanson’s teams have characterised a new gene, TCF12, involved in the development of an aggressive form of brain cancer, anaplastic oligodendrogliomas. Inactivation of this transcription factor leads to the loss of expression of tumour suppressing genes, and would be associated with greater tumour agressivity. This discovery opens a new perspective in understanding the development of these tumours and identifying their causes. It gives hope in the longer term for a personalised treatment on the basis of this molecular alteration.

New genes involved in oligodendrogliomas : CIC

60 % of oligodendrogliomas show a CIC mutation, a transcription repressor (one of the stages allowing to skip from DNA to protein). Vincent Gleize in Marc Sanson’s team, has elucidated this gene’s action mechanisms within tumour cells. CIC inactivation leads to an accumulation of proteins involved in cell proliferation. This accumulation leads to tumour formation. Identify these mechanisms is the first step towards the identification of potential therapeutic targets.

Hope for a personalised treatment of glioblastomas

Through the Gliotex experimental therapy platform (supported by the ARC Foundation for Cancer Research and by the Brain Tumour Research Association), co-directed by Ahmed Idbaih and Jean-Yves Delattre, specific therapies are implemented according to the tumour mutation profile. In this context, Marc Sanson’s team has tested an inhibitor targeting the oncogene, MDM2, which leads to gene amplification in some tumours. Cells with this mutation respond electively to this inhibitor. These results are very encouraging for the development of personalised therapies in human and give hope for the establishment of a phase 1 clinical trial.

A new meningioma preclinical model reproducing faithfully human pathology

Meningiomas are the most frequent primary tumours of the central nervous system in adults over 35. Most of these tumours are benign but some can be more aggressive with multiple recurrences. Michel Kalamarides and Matthieu Peyre have been developing meningioma preclinical models for a long time. They have just shown that inactivation of certain genes, Nf2 and Cdkn2ab, as well as activation of PDGF-β growth factor at the level of meningeal cells produced fast growing meningiomas in mouse (high grade). This unique model will enable them to test new patient promising therapeutic approaches.

New targets identified in cerebral primitive lymphomas

Khe Hoang-Xuan has identified specific and common mutations in primitive lymphomas of the central nervous system affecting MYD88 and CD79B genes. These mutations activate two signalling pathways which seem to play an important role in these lymphomas genesis. Not only are they diagnostic biomarkers, but they also pave the way for targeted innovative therapy trials.

CLINICAL RESEARCH

A specific and customised therapy

A clinical trial,  » TARGET « , coordinated by Marc Sanson has begun on a national level and could be extended at European level. It aims at testing a specific and customised therapy on patients with glioblastomas expressing a highly oncogenic anomaly, in other words, responsible for tumour development. This study is carried out in partnership with Astra-Zeneca and the Assistance Publique-Hôpitaux de Paris.

An oncolytic virus trial

A phase I clinical trial, « ONCOVIRAC », led by Ahmed Idbaih, testing an oncolytic virus, that is, a virus modified to specifically destroy cancer cells in patients with glioblastoma, will soon begin. This trial is the result of a partnership between the Transgène company, which has developed the virus and the Assistance Publique-Hôpitaux de Paris.

An MRI non-invasive diagnostic method

IDH1 gene mutation is specific to gliomas, and affects 40 % of them. It plays a major role in the development of these tumours and is characterised by the accumulation of a metabolite, D-2HG, in the tumour. The  » IDASPE  » trial, coordinated by Marc Sanson and conducted in collaboration with the CENIR, has developed detection of D-2HG in the tumour by MRI spectroscopy, thus providing a non-invasive diagnostic tool that may soon be used clinically.

RESEARCH DEVELOPMENT

Extended release of anti-cancer molecules

GECKO BIOMEDICAL, led by Christophe Bancel, develops a technology enabling anti-cancer molecule extended release in surgery for glioblastoma applications.

Ultrasound, a revolution in brain tumour treatment ?

Through ultrasound use, it is possible to open the blood-brain barrier-on-demand to enable drugs to enter brain diseased areas. The SonoCloud® device was developed by the CarThera company, located at the ICM, on the basis of Professor Alexandre Carpentier’s works, neurosurgeon at the Pitié Salpêtrière hospital. This breakthrough will significantly increase drug efficiency, which today can’t cross the blood-brain barrier protecting brain tissue. This could make brain tumour and neurodegenerative disease treatment much more efficient. Phase 1 clinical trials are currently ongoing.