E. Cohen-Jonathan Moyal / C. Toulas

  Glioblastoma radioresistance: from signaling pathways to clinical trials

 

 

 

 

 

 

Our research project at a glance

 

Our team is a translational research team specialized in optimizing the radiotherapy treatment of glioblastoma (GBM). We first decipher the biological mechanisms of GBM radioresistance, then perform preclinical and clinical trials to evaluate the efficiency of combining radiotherapy with specific inhibitors of the radioresistance mechanisms we previously identified.  We focus our research more particularly on the role of GBM stem cells in the tumor radioresistance.

 

Objectives

 

Our team is a translational research team in radiobiology, specialized in optimizing the radiotherapy treatment of glioblastoma (GBM). Our research is conducted in 3 complementary approaches:

  • first by deciphering the biological mechanisms of tumor radioresistance,
  • by performing preclinical trials to validate targets for new radiosensitizer agents and to identify new predictive markers,
  • finally by conceiving and performing early phase clinical trials performed in our Institute (IUCT) associating targeted drugs directed against the target identified in the lab with radiotherapy and integrating metabolic imaging studies, as well as surrogate biomarkers.

This 3-axis strategy to improve the GBM radiotherapy treatment efficiency is now amplified by strengthening our research on tumor heterogeneity and more particular on GBM radiation-induced migration and plasticity as well as GBM stem cells (GSC) involvement in GBM radioresistance.

This team also pursues its investigation concerning the mechanisms sustaining glioblastoma differentiated cells radioresistance by investigating the role of microenvironment factors as integrins and growth factors.

 

Key words

 

  • Glioblastoma
  • Resistance to radiotherapy
  • Stem cells

 

Selected publications


2017

Deutsch, E; Moyal, E C; Gregorc, V; Zucali, P A; Menard, J; Soria, J C; Kloos, I; Hsu, J; Luan, Y; Liu, E; Vezan, R; Graef, T; Rivera, S

A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors Journal Article

Oncotarget, 8 (34), pp. 56199-56209, 2017, ISSN: 1949-2553 (Electronic) 1949-2553 (Linking).

Links | BibTeX

Kast, R E; Skuli, N; Karpel-Massler, G; Frosina, G; Ryken, T; Halatsch, M E

Blocking epithelial-to-mesenchymal transition in glioblastoma with a sextet of repurposed drugs: the EIS regimen Journal Article

Oncotarget, 8 (37), pp. 60727-60749, 2017, ISSN: 1949-2553 (Electronic) 1949-2553 (Linking).

Links | BibTeX

Kowalski-Chauvel, A; Gouaze-Andersson, V; Vignolle-Vidoni, A; Delmas, C; Toulas, C; Cohen-Jonathan-Moyal, E; Seva, C

Targeting progastrin enhances radiosensitization of colorectal cancer cells Journal Article

Oncotarget, 8 (35), pp. 58587-58600, 2017, ISSN: 1949-2553 (Electronic) 1949-2553 (Linking).

Links | BibTeX

2016

Goldbrunner, R; Minniti, G; Preusser, M; Jenkinson, M D; Sallabanda, K; Houdart, E; von Deimling, A; Stavrinou, P; Lefranc, F; Lund-Johansen, M; Moyal, E C; Brandsma, D; Henriksson, R; Soffietti, R; Weller, M

EANO guidelines for the diagnosis and treatment of meningiomas Journal Article

Lancet Oncol, 17 (9), pp. e383-91, 2016, ISSN: 1474-5488 (Electronic) 1470-2045 (Linking).

Links | BibTeX

Gouaze-Andersson, V; Delmas, C; Taurand, M; Martinez-Gala, J; Evrard, S; Mazoyer, S; Toulas, C; Cohen-Jonathan-Moyal, E

FGFR1 Induces Glioblastoma Radioresistance through the PLCgamma/Hif1alpha Pathway Journal Article

Cancer Res, 76 (10), pp. 3036-44, 2016, ISSN: 1538-7445 (Electronic) 0008-5472 (Linking).

Links | BibTeX

2015

Najib, S; Kowalski-Chauvel, A; Do, C; Roche, S; Cohen-Jonathan-Moyal, E; Seva, C

Progastrin a new pro-angiogenic factor in colorectal cancer Journal Article

Oncogene, 34 (24), pp. 3120-30, 2015, ISSN: 1476-5594 (Electronic) 0950-9232 (Linking).

Links | BibTeX

Sesen, J; Dahan, P; Scotland, S J; Saland, E; Dang, V T; Lemarie, A; Tyler, B M; Brem, H; Toulas, C; Cohen-Jonathan Moyal, E; Sarry, J E; Skuli, N

Metformin inhibits growth of human glioblastoma cells and enhances therapeutic response Journal Article

PLoS One, 10 (4), pp. e0123721, 2015, ISSN: 1932-6203 (Electronic) 1932-6203 (Linking).

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2014

Ader, I; Delmas, C; Skuli, N; Bonnet, J; Schaeffer, P; Bono, F; Cohen-Jonathan-Moyal, E; Toulas, C

Preclinical evidence that SSR128129E--a novel small-molecule multi-fibroblast growth factor receptor blocker--radiosensitises human glioblastoma Journal Article

Eur J Cancer, 50 (13), pp. 2351-9, 2014, ISSN: 1879-0852 (Electronic) 0959-8049 (Linking).

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Dahan, P; Martinez Gala, J; Delmas, C; Monferran, S; Malric, L; Zentkowski, D; Lubrano, V; Toulas, C; Cohen-Jonathan Moyal, E; Lemarie, A

Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance Journal Article

Cell Death Dis, 5 , pp. e1543, 2014, ISSN: 2041-4889 (Electronic).

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2013

Lanvin, O; Monferran, S; Delmas, C; Couderc, B; Toulas, C; Cohen-Jonathan-Moyal, E

Radiation-induced mitotic cell death and glioblastoma radioresistance: a new regulating pathway controlled by integrin-linked kinase, hypoxia-inducible factor 1 alpha and survivin in U87 cells Journal Article

Eur J Cancer, 49 (13), pp. 2884-91, 2013, ISSN: 1879-0852 (Electronic) 0959-8049 (Linking).

Links | BibTeX