Every year in France, about 1000 to 2000 people are diagnosed with glioblastoma. Glioblastoma is the most frequent and serious malignant brain tumour in adults. New treatments are necessary to improve survival and quality of life of these patients. Every year, new precision drugs and innovating therapeutic strategies emerge, several of which could be efficacious in patients suffering from glioblastoma.
The academic research group GlioTex, co-directed by Pr Jean-Yves Delattre and Dr Ahmed Idbaih, is part of the Experimental Neuro-Oncology team directed Pr Marc Sanson and located at the Brain and Spine Institute at the university hospital La Pitié-Salpêtrière.
With the objective of accelerating the preclinical evaluation of new therapeutic approaches towards the clinic, GlioTex group has established more than 50 cell line models and murine models of human glioblastoma derived from the tumour of patients operated at La Pitié-Salpêtrière. The efficacy of innovating compounds is evaluated in these models by assessing cell viability and proliferation. GlioTex cell lines are characterized at the molecular level by high throughput molecular biology approaches (whole exome and whole transcriptome sequencing) allowing, for instance, to perform correlations between certain molecular alterations and response to compounds. Further, the therapeutic efficacy of compounds can be evaluated in immunosuppressed mice xenografted in orthotopic position. Mice can then be treated by intravenous, intraperitoneal or oral routes. In these assays, GlioTex monitors survival and tumour growth by magnetic resonance or bioluminescence imaging. Biological tissues (brain, plasma, tumour) can be harvested for pharmacokinetic or pharmacodynamic studies. Promising results can support the conduction of early clinical trials in patients suffering from glioblastoma.
The project GlioTex thus allows establishing a therapeutic highway aiming to bring as fast as possible the most promising innovating therapeutic strategies from the lab bench to patients’ bedside.
Group members:
Ahmed Idbaih, principal investigator
Jean-Yves Delattre, co-principal investigator
Maïté Verreault, researcher and scientific manager
Jérémy Guehennec, study engineer and manager-assistant
Nolwenn Lemaire, study engineer assistant
References:
Verreault M, Schmitt C, Goldwirt L, Pelton K, Haidar S, Levasseur C, Guehennec J, Knoff D, Labussière M, Marie Y, Ligon AH, Mokhtari K, Hoang-Xuan K, Sanson M, Alexander BM, Wen PY, Delattre JY, Ligon KL, Idbaih A. Preclinical Efficacy of the MDM2 Inhibitor RG7112 in MDM2-Amplified and TP53 Wild-type Glioblastomas. Clin Cancer Res. 2016 Mar 1;22(5):1185-96. doi: 10.1158/1078-0432.CCR-15-1015. Epub 2015 Oct 19
Rosenberg S, Verreault M, Schmitt C, Guegan J, Guehennec J, Levasseur C, Marie Y, Bielle F, Mokhtari K, Hoang-Xuan K, Ligon K, Sanson M, Delattre JY, Idbaih A. Multi-omics analysis of primary glioblastoma cell lines shows recapitulation of pivotal molecular features of parental tumors. Neuro Oncol. 2017 Feb 1;19(2):219-228. doi: 10.1093/neuonc/now160.
Dréan A, Goldwirt L, Verreault M, Canney M, Schmitt C, Guehennec J, Delattre JY, Carpentier A, Idbaih A. Blood-brain barrier, cytotoxic chemotherapies and glioblastoma. Expert Rev Neurother. 2016 Nov;16(11):1285-1300. Epub 2016 Jul 4.
Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran DD, Brem S, Hottinger AF, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Burna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316.
Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med. 2017 Nov 16;377(20):1954-1963.
Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C, Karachi C, Leclercq D, Lafon C, Chapelon JY, Capelle L, Cornu P, Sanson M, Hoang-Xuan K, Delattre JY, Idbaih A. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016 Jun 15;8(343):343re2.
Gliotex is also committed as part of the European consortium GLIOTRAIN to address European research training needs in translational brain tumour research, cancer systems medicine and integrative multi-omics.
Support:
GlioTex project and group was supported by Fondation ARC pour la recherche sur le Cancer.
GlioTex project is now supported by the Brain and Spine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne Université, Institut Universitaire de Cancérologie (IUC) and Association pour la Recherche sur les Tumeurs Cérébrales.