CNRS

Description of the legal entity:

The legal entity that will be responsible of administrative part is the CNRS (Centre National de la recherche scientifique, http://www.cnrs.fr/fr/page-daccueil). The National Center for Scientific Research is one of the most important research institutions in the world. To meet the great challenges present and to come, his scientists are exploring the living, the matter, the universe and the functioning of human societies. Internationally recognized for the excellence of its scientific work, the CNRS is a reference in the world of research and development as well as for the general public. The CNRS celebrates its 80^th anniversary this year.

The project will be performed at the “Institute for Research on Cancer and aging of Nice (IRCAN, http://ircan.org/). The laboratory has multi-legal entities including the CNRS, Inserm Institut National de la Santé et de la Recherche Medicale, https://www.inserm.fr/) and University Cote D’azur (http://univ-cotedazur.fr/). IRCAN has also a partnership with the Cancer Centre of Nice, The Centre Antoine Lacassagne (CAL, https://www.centreantoinelacassagne.org) which belongs to the Fédération of Cancer Centres in France. The CAL is renown worldwide for the tre,atment by proton therapy. The Center is now equipped with the last generation of pulse field proton therapy.

IRCAN is composed of 17 independent teams and has focused on obtaining the best working conditions with more than 150 most of the best international researchers, engineers and technicians. The latest scientific equipment, such as molecular and cellular microscopy, cytometry and genomic analysis, a common tumour bank to the hospital center and the anti-cancer center of Nice, are also available.

CNRS will be responsible of the work package “Risk factor associated with lymphedema: chemotherapy and radiotherapy”. The team of Gilles Pagès focused its research on the regulation of angiogenic factors and their role as markers of sensitivity or resistance to treatments in different cancers. The first major paper of the team was published in Blood in 2004 for the efficacy of Gleevec in chronic myeloid leukemia; (Legros, L et al). More recently the team has focused on renal cell carcinoma and has published pivotal papers on the mechanisms of resistance to anti-angiogenic drugs (Grépin R et al Oncogene 2012, Cancer Res 2014; PlosOne 2014; Giuliano, S et al Autophagy 2015 and Theranostics, 2019, Dufies M et al Cancer Res 2017, BJC 2017, BJC 2018, Theranostics 2018; Ndiaye P Theranostics 2019). We also published a pivotal paper for the comparison of radiotherapy photons or protons and their relative efficacy for the treatment of head and neck carcinoma (Lupu-Plesu et al Oncogenesis 2017).

CNRS Main tasks in the project per WP

• WP1: CNRS is WP leader and implicated in Effect of photon radiation on the lymphatic endothelium in vitro (Task 1.1) Effect of photon/proton radiation on the lymphatic endothelium in vivo ( Tasks 1.2) and Effect of radiation on VEGFC synthesis (Tasks 1.3)

WP9 CNRS will contribute to dissemination and communication activities.

Curriculum Vitae:

Dr. Gilles Pagès (Male):

Gilles  PAGES, is a principal investigator at IRCAN. He is the author of 140 publications in Science, Nature Cell Biol, Immunity, Neuron, PNAS, Blood, Cancer Res, Circulation, Human Mol Genet, J Biol Chem, PlosOne, etc. H factor 52. Authors of 9 patents and one licence.

Gilles Pagès is the current president of the French Society of Angiogenesis, an elected member of the National committee Cancer and translational research (CSS2) of INSERM, and a Member of the administrative council of the European Vascular Biology Organization (EVBO)

Dr Maeva Dufies (Female): 

Dr Dufies is a specialist of the mechanisms of resistance to anti-angiogenic treatments. She performed several translational studies to discover plasmatic markers that predict drug responses. She published 6 paper in the last years and obtained two patents

Dr. Sandy Giuliano (Female):

Dr Giuliano discovered that several drugs used as chemotherapeutic agent are trapped in lysosomes. She is an expert of this specific mechanisms that can be implemented for several cancers. She published her first paper on this topic on renal cells carcinoma (Autophagy 2015) and she implemented her discovery in breast cancers (Theranostics 2019).

List of up to 5 relevant publications, and/or products, services (including widely-used datasets or software), or other achievements relevant to the  call content

• Giuliano, S, Dufies, M, Diogop Ndiaye, P, Viotti, J, Borchiellini, D, Parola, J, Vial, V, Cormerais, Y, Ohanna, M, Imbert, V, Chamorey, E, Rioux-Leclercq, N, Savina, A, Ferrero, JM, Mograbi, B and Pagès, G. Resistance to lysosomotropic drugs used for kidney and breast cancers involves autophagy and inflammation and converges in inducting CXCL5Theranostics, 2019 9 (4): 1181-1199.
• Ndiaye PD, Dufies M, Giuliano S, Douguet L, Grépin R, Durivault J, Lenormand P, Glisse N, Mintcheva J, Vouret-Craviari V, Mograbi B, Wurmser M, Ambrosetti D, Rioux-Leclercq N, Maire P, Pagès G. VEGFC acts as a double-edged sword in renal cell carcinoma aggressiveness. Theranostics2019; 9(3):661-675.

• Plesu, M*, Claren, A*, Martial, S, Diogop N’Diaye, P, Lebrigand, K, Pons, N, Ambrosetti, D, Peyrottes, I, Feuillade, J, Hérault, J,  Dufies, M,  Doyen. J and Pagès, G. Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma, Oncogenesis 2017 3;6(7):e354.
• Dufies M, Giuliano S, Ambrosetti D, Claren A, Diogop Ndiaye P, Mastri M, Moghrabi W, Cooley LS, Ettaiche M, Chamorey E, Parola J, Vial V, Lupu-Plesu M, Bernhard JC, Ravaud A, Borchiellini D, Ferrero JM, Bikfalvi A, Ebos JM, Khabar KS, Grepin R, Pagès G. Sunitinib stimulates expression of VEGFC by tumor cells and promotes lymphangiogenesis in clear cell renal cell carcinomas. Cancer Res. 2017 Mar 1;77(5):1212-1226

List of up to 5 relevant previous projects or activities, connected to the subject of this proposal

• VELYMPH project FP7 VEGFC and the link with resistance to radiotherapy 300 kE (2016-2017)
• National Cancer Institute (INCA) France Mechanism of resistance to anti-angiogenics (500 kE) (2017-2019)
• National Research Agency (ANR) France Targeting the ELR+CXCL cytokines and their receptors (500 kE) (2018-2021)
• The Ligue Nationale contre le Cancer France, VEGFC: Beneficial and Pejorative Roles in Metastatic Dissemination and Mechanisms of Resistance to Radio / Chemotherapy Treatments; Expression regulation and therapeutic targeting at optimal time (300 kE) (2019-2021)

Infrastructure and/or major items of technical equipment

Facilities available in the institute for research on cancer and aging of Nice (IRCAN http://ircan.bit2bit.it/en/about-the-ircan/presentation) and required for the project include Genomic (qPCR Applied StepOne Plus, Applied 7500, Applied 7900HT, Biomolecule quantification NanoDrop 2000, Bioanalyzer 2100, Qubit 2.0 Next generation sequencing  on OneTouch System (Life Technologies), Ion Torrent PGM Bioassays  Luminex 100/200, Vitros 350,Microscopy (AFM microscope, Inverted Confocal Microscope ZEISS LSM Exciter, ZEISS High-throughput Live Epi-fluorescence Microscope, ZEISS Time Lapse Epi-fluorescence Microscope, ZEISS Epi-fluorescence Cytogenetics Microscope), Cell sorting/Cytomery platform (FacsAria, FacsCanto, SeaHorse XF24 3 Bioscience) and Animal houses specific for patients derived xenografts.

The Centre Antoine Lacassagne is an European reference Center for radiotherapy (https://www.centreantoinelacassagne.org/qui-sommes-nous/les-poles/departement-de-radiotherapie/) . The center acquired recently the last generation of proton pulse radiotherapy (https://iba-worldwide.com/proton-therapy).

Operational capacity

Fully operational