Master II Research, Cellular and Molecular Biology, Blaise-Pascal University, Clermont-Ferrand, FRANCE, 2005
PhD Cellular and Molecular Biology: “Role of Interleukin-6 signaling pathway in human glioblastoma radioresistance” 2009. Team EA3846, Auvergne University.
Research Engineer in Team CREaT : Cancer Resistance Exploring and Targeting . Identification and neutralization of molecular targets involved in human glioblastoma radioresistance.(Jean Perrin Anticancer Center, Auvergne University, CHU Clermont-Ferrand)
During PhD :
Identification and neutralization of molecular targets involved in human glioblastoma radioresistance mechanism is an approach developed in the laboratory to decrease recurrence inside irradiated volume and then to increase patient survival. Previous data published by the team have demonstrated a potential role of interleukin-6 (IL-6) in anti-apoptotic mechanism involved in radioresistance. Firstly, we contributed to IL-6 validation as a potential target by demonstrating association between amplification with overexpression of IL-6 gene and a bad prognosis in 36 glioblastoma. Median survival dropped from 22 to 6 months between IL-6 non-amplified and amplified group. Although, we have found no correlation between intrinsic radioresistance and expression or IL-6 production in vitro, published data prompted us to explore therapeutic potential of blocking IL-6 downstream signaling pathways such as PI3K/Akt and JAK/STAT3. Akt pathway inhibition, whose activation has been correlated with intrinsic radioresistance, radiosensitizes glioblastoma in vitro whereas STAT3 inhibition did not affect ionizing radiation sensitivity. Accordingly, second approach using antibodies against IL-6 or its receptor subunits induced a decrease in STAT3 pathway activation without any effect on radioresistance. Results provided by this work suggest that IL-6, despite being a prognosis factor, and STAT3 pathway are not involved in intrinsic radioresistance. Our hypothesis is that in glioma, frequently activated STAT3 pathway is involved in microenvironment alteration such as immunosuppression and angiogenesis as described in the literature.
On Going activities :
1) Identification of molecular mechanisms involed in glioma radioresistance : basal and radio-induced survival pathway (PI3K/Akt, IL-6/STAT3 pathways).
2) Disturb DNA repair for radiosensitizing glioma by targeting telomeric functions with G4-ligands and double strand DNA repair with "Dbait".