Research topics

Introduction
Radiotherapy is one of the basis treatments to fight cancer and is used in almost 60% of the clinical trials. If some cancers are refractory to radiation treatments, two major scientific advances must overpass this tumor radioresistance :
• Non-cancerous cells in the tumor microenvironment contribute to tumor growth and response to anticancer treatments. They should be considered as therapeutic targets in the same way as cancer cells. Among these microenvironmental cells, endothelial cells by forming blood vessels contribute to the nutrient supply of tumors and immune cells participate in the recognition and destruction of tumor cells.
• Technological innovations in physics and imaging make it possible to deliver high doses of radiation in a highly targeted manner to the tumor. They promote the development of new radiotherapy protocols, including high dose hypofractioned radiation therapy (RT-Hypo), with limited toxicity to healthy peritumoral organs.

Aims and Objectives
In this context, “Radiobiology and Targeting the Endothelium” team in the CRCINA search to better understand the responses of the vascular and immune microenvironment involved in tumor sensitivity to new radiotherapy protocols. By characterizing the main actors, the main objective is to optimize and adapt new radiotherapy strategies, including RT-Hypo or combination radiotherapy / immunotherapy. The discovery of these actors will also allow the development of new biomarkers that are predictive of the response to treatments for better personalization of radiotherapy protocols.

Projet
To carry out this project, the team integrates researchers with complementary skills in basic biology and radiobiology, immunology and antibody development, physical medicine and clinical radiation oncology. We concentrate our work on 4 cancers already treated by radiotherapy and requiring new therapeutic protocols: prostate cancer, glioblastoma, and breast cancer, as well as neuroblastoma as pediatric cancer. The research project is divided into 3 sections :

1) Understanding biological mechanisms induced in the vascular system and involvement in the tumor response after radiotherapy

2) Understanding the biological mechanisms induced in the immune system and involvement in the tumor response after radiotherapy

3) Application to Optimization of Radiation Therapy and Cancer Immunotherapy

En savoir plus :

Equipe 14

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Contact

  • François Paris
  • Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
  • Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1
  • +33 2 28 08 03 02
  • francois.paris@inserm.fr

Graphic Resume

Equipe 14 : Microenvironment radiobiology & targeting

Technologic development

Project Manager

Dr. Sophie Fougeray, Pharm.D./Ph.D., Maître de conférences des universités, Faculté de Pharmacie
Projet : Optimisation d’un protocole combinant la radiothérapie et l’immunothérapie anti-OAcGD2 dans le gliobastome

Dr. Sophie Chiavassa, Ph.D., Physicien médical, Institut de Cancérologie de l’Ouest
Projet : Physique et Modèle d’irradiation du petit animal

Dr. Gregory Delpon, Ph.D., Physicien médical, Institut de Cancérologie de l’Ouest
Projet : Physique médical translationnelle

Dr. Stéphane Supiot, M.D./Ph.D., Radiothérapeute, Maître de conférences des universités,  Praticien hospitalier, Faculté de Médecine & Institut de Cancérologie de l’Ouest
Projet : impact du remodelage vasculaire radioinduit dans la réponse anti-tumorale

Dr. Stéphane Birklé, D.V.M./Ph.D., Professeur des universités, Faculté de Pharmacie
Projet : Immunothérapie anti-OAcGD2 contre le neuroblastome

Dr. François Paris, Ph.D., DR2 Inserm
Projet : Réponse paracrine des cellules endothéliales irradiées et

Organigram

F. Paris, DR INSERM
S. Birklé, PU-Univ. Nantes
S. Fougeray, MCU-Univ. Nantes
S. Supiot MCU-PH – ICO
G. Delpon, PH – ICO
S. Chiavassa, PH – ICO
D. Leonetti, Post doctorant
V. Potiron, Post doctorant
N. Dubois, IR, ICO
M. Pietri, IE, INSERM
M. Guillonneau, IE, INSERM
J. Fleurence, Doctorant
K. Clement-Colmou, Doctorant
C. Degorre , Doctorant
S. Faraj, Doctorant
M. Bahri, Doctorant
H. Estephan, Doctorant
S. Joseph, Master 2
V. Libois, Master 2
M. Nedellec, Master 2

Chercheurs Associés
E. Rio, PH-ICO
A. Lisbona, PH-ICO
E. Thebaud, PH-CHU

Funding

Publications 2012-17

1. Desselle A, Chaumette T, Marie-Hélène Gaugler MH, Cochonneau D, Fleurence J, Dubois N, Hulin P, Aubry J, Birklé S, Paris F. Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development. Plos One. (2012)

2. Supiot S., Paris F. Radiobiologie appliquée à l’endothélium. Cancer Radiother. (2012)

3. Almaghrabi MY, Supiot S, Paris F, Mahé MA, Rio E. Stereotactic Body Radiation Therapy for Abdominal Oligometastases: A biological and clinical review. Radiat Oncol. (2012)

4. Potiron V, Abderrhamani R, Giang E, Chiavassa S, Di Tomaso E, Maira S-M, Paris F, Supiot S. Radiosensitization of prostate cancer cells by the dual PI3K/mTOR inhibitor BEZ235 under normoxic and hypoxic conditions. Radiother Oncol. (2013)

5. Oliver L, Hue E, Séry Q, Lafargue A, Pecqueur C, Paris F, Vallette FM. Differentiation Related Response to DNA Breaks in Human Mesenchymal Stem Cells. Stem Cells. (2013)

6. Cochonneau D, Terme M, Michaud A, Dorvillius M, Gautier N, Frickeche J, Alvarez-Rueda N, Bougras G, Aubry J, Paris F, Birklé S. Cell cycle arrest and apoptosis induced by O-Acetyl-GD2-specific monoclonal antibody 8B6 inhibits tumor growth in vitro and in vivo. Cancer Letters. (2013)

7. Birklé S, Desselle A, Chaumette T, Gaugler M.H, Cochonneau D, Fleurence J, Dubois N, Hulin P, Aubry J, and Paris F. Inhibition of tumor angiogenesis by globotriaosyl ceramide Gb3 immunotargeting. Oncoimmunology. (2013)

8. Noblet C, Chiavassa S, Paris F, Supiot S, Lisbona A, Delpon G. Underestimation of dose delivery in preclinical irradiation due to scattering conditions. Phys Med. (2014)

9. Potiron VA, Abderrahmani R, Clément-Colmou K, Marionneau-Lambot S, Oullier T, Paris F, Supiot S. Improved functionality of the vasculature during conventionally fractionated radiation therapy of prostate cancer. PLoS One. (2013)

10. Corre I, Guilloneau M, Paris F. Membrane signaling induced by high doses of ionizing radiation in the endothelial compartment. Relevance in radiation toxicity. Int J Mol Sciences. (2013)

11. Terme M, Dorvillius M, Cochonneau D, Chaumette T, Xiao W, Diccianni MB, Barbet J, Yu AL, Paris F, Sorkin LS, Birklé S. Chimeric Antibody c.8B6 to O-Acetyl-GD2 Mediates the Same Efficient Anti-Neuroblastoma Effects as Therapeutic ch14.18 Antibody to GD2 without Antibody Induced Allodynia. PLoS One. (2014)

12. Mignard V, Lalier L Paris F, Vallette FM. Bioactive Lipids and the control of Bax/ Bak pro-apoptotic activity. Cell Death Disease,  (2014)

13. Brocard E, Oizel K, Lalier L, Pecqueur C, Paris F, Vallette FM, Oliver L. Radiation-induced PGE2 sustains human glioma cells growth and survival through EGF signaling. Oncotarget. (2015)

14. Noblet C, Chiavassa S, Smekens F, Sarrut D, Passal V, Suhard J, Lisbona A, Paris F, Delpon G. Validation of fast Monte Carlo dose calculation in small animal radiotherapy with EBT3 radiochromic films. Phys Med Biol. (2016)

15. Dubois N, Rio E, Ripoche E, Ferchaud-Rouche V, Gaugler MH, Campion L, Krempf M, Carrie C, Mahé M, Mirabel X, Paris F. Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan. Radiother Oncol. (2016)

16. Silva V, Lafont F, Benhelli-Mokrani H, LeBreton M, Hulin P, Chabot T, Paris F, Sakanyan V, Fleury F. Rapid diminution in the level and activity of DNA-dependent protein kinase in cancer cells by a reactive nitro-benzoxadiazole compound. Int. J. Mol Sciences. (2016)

17. Guillonneau M, Paris F, Dutoit S, Estephan H, Bénéteau E, Huot J, Corre I. Oxidative stress disassembles the p38 /NPM/PP2a complex leading to the modulation of NPM-mediated signaling to DNA damage response. FASEB. (2016)

18. Fleurence, J, Cochonneau D, Fougeray S, Oliver L, Geraldo F, Dorvillus M, Loussouarn D, Vallette F, Paris F, Birkle S. Targeting and killing glioblastoma with monoclonal antibody to O-acetyl-GD2 ganglioside. Oncotarget. (2016)

19. Fadous-Khalifé MC, Aloulou N, Jalbout M, Hadchity J, Aftimos G, Paris F, Hadchity E. Krüppel-like factor 4: A new potential biomarker of lung cancer. Mol Clin Oncol. (2016)

20. Niaudet C, Bonnaud S, Guillonneau M, Gouard S, Gaugler MH, Dutoit S, Ripoche N, Dubois N, Trichet V, Corre I, Paris F. Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38 MAPK pathways in endothelial cells apoptosis. Cell. Signaling. (2017). Accepted

21. Fleurence J, Fougeray S, Bahri M, Cochonneau D, Clémenceau B, Paris F, Heczey A, Birklé S. Targeting O-Acetyl-GD2 Ganglioside for Cancer Immunotherapy. J Immunol Res. (2017). Accepted