TGFβ signaling, Glutathione homeostasis & Innovative therapies in Cancer
The Team TGTC gathers basic researchers and hospital practitioners with a common interest and complementary expertise in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and pancreatic ductal adenocarcinoma (PDAC). These are aggressive cancers with rising incidence, poor prognosis and limited therapeutic options. Tumor onset and progression are associated with drastic changes in the tumor microenvironment modulating key signaling pathways which contribute to carcinogenesis, and high intracellular glutathione (GSH) content promoting cancer cell survival and proliferation.
The general objective of the team is to better understand changes in the tumor microenvironment and their impact on tumor cell biology to provide new therapeutic orientations in cancer. We explore this issue by using two paradigms, namely the TGFβ signaling and GSH homeostasis. In this context we aim at better characterizing the contextual determinants that shape the TGFβ pathway in normal and cancer cells to provide a rationale for efficient targeted therapies using TGFβ inhibitors. Notably, we explore the role of novel effectors and regulators of the TGFβ pathway in cancer, including long non coding RNA. We also address the contribution of the cystine/glutamate xCT antiporter in the intracellular levels of cysteine, the main limiting factor in GSH biosynthesis, in normal liver and HCC and the role of the GSH homeostasis in tumor cell survival and growth.
At a translational and clinical level, our objectives include: i) the identification of non-invasive companion biomarkers for targeted therapies and prognosis biomarkers, ii) the evaluation of new clinical approaches to prevent tumor recurrence and iii) the development of synthetic nanovectors for tumor drug delivery, in collaboration with the National School of Chemistry in Rennes, and metabolic radiotherapy.
TGFβ signaling, immunity in liver & pancreatic carcinogenesis:
- S. Dooley (Heidelberg Univ., Germany)
- W. Mikulitz (Cancer Res. Institute, Vienna, Austria)
- Gomez-Quiroz (Mexico City)
- C. Perret & H. Gilgenkrantz (Cochin Institute, Paris)
- A. Herbelin (Inserm U1082, Poitiers)
- P. Jeannin (U892, Angers)
- E. Scotet (U892, Nantes)
- V. Gouilleux (UMR CNRS 7292, Tours)
- L. D. Malka (Gustave Roussy, Villejuif)
- J.M. Phelip (CHU St. Etienne)
- J.F. Blanc (CHU Bordeaux)
- J. Bridgewater (Univ. College London, UK)
- T. Meyer (University College London, UK)
- B. Sangro (Univ. Clinic, Pamplona, Spain)
- O. Farges & N. Benderski (Bichat-Beaujon hospital, Paris).
Role of GSH and cardiolipins in hepatic cells:
- S. Servais (INSERM U1069-Nutrition Croissance et Cancer, CHU Tours)
- A. Rébillard (laboratoire M2S, ENS Cachan, Campus de Kerlan, Rennes).
Vectorization & metabolic radiotherapy:
- S. Guillaume (Institute of Chemistry, CNRS UMR 6226, Rennes)
- T. Montier (Inserm U1078, Brest)
- N. Noiret (ENSCR, UMR CNRS 6226, Rennes)
- R. Lebtahi, (Beaujon Hospital, Paris)
- F. Hindré & F. Lacœuille (Univ. Angers, UMR INSERM 1066)
- J.P. Benoist (Univ. Toulouse, SPCMIB UMR CNRS 5068)
- J.M. Chezal & E. Miot-Noirault (Univ. Clermont-Ferrand, UMR INSERM 990)
- C.H. Malbert (INRA, Plateforme Ani-Scans UR1341 ADNC, St Gilles)
- S. Huclier-Markai (Arronax, St Herblain)
- A. Shinto (Coimbatore Hospital, India)
- C. Chiesa (Milan Hospital, Italia)
- R. Salem (Northwestern Univ., USA)
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