Team
Gilles Favre – Olivier Sordet
SIGNATHER :
Cell Signalling, Oncogenesis and Therapeutics
The specificities
of our research axis
Our general aim is to understand the molecular abnormalities of cancer cell signaling pathways and to translate these laboratory results into the development of new therapeutic strategies. We focus first on the receptor tyrosine kinase (RTK)/RAS/MAPK and RHOGTPase pathways to understand their connections with the control of cell proliferation, survival and tumor progression, and to design new therapeutic strategies. We also study the signaling and repair mechanisms of DNA double-strand breaks (DSB) generated in transcribed regions, and their cross-talk with oncogenic signaling, to understand their role in oncogenesis and resistance to targeted therapies. Team strengths in the leading-edge biotechnologies of GFP-based protein/protein interaction contribute to the discovery of new biological and clinical findings. Expertise in signal transduction and DNA damage response pathway has contributed directly and indirectly to new concepts in the resistance to targeted therapies and new target discovery. In close collaboration with clinical departments, we develop translational and clinical research in lung cancers.
Oncogenic signaling
RTK/RAS/MAPK
RHOGTPases
Lung cancer
Translational research
Liquid biopsies
Biomarkers
Clinical trials
Targeted therapy
REsistance
BiotechnologY
Split GFP
DNA break
Genome instability
Transcription
rESEARCH
PROJECTS
Exploring transcription in oncogenesis and response to anticancer treatment
Agnese Cristini
Transcriptional DNA breaks and human disease
Olivier Sordet
Early detection of cancer and of treatment resistance
Anne Pradines and Julien Mazières
Rho-mediated cellular plasticity during lung cancer progression and resistance to therapy
Olivier Calvayrac
Molecular mechanisms and modulation of small GTPase activity in cancer
Stéphanie Cabantous
THE TEAM’S
FOCUS
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SCIENTIFIC PRODUCTIONS
PUBLICATIONS 2023
Martins, Carla Silva, Cyntia Taveneau, Gerard Castro-Linares, Mikhail Baibakov, Nicolas Buzhinsky, Mar Eroles, Violeta Milanović, et al. “Human Septins Organize as Octamer-Based Filaments and Mediate Actin-Membrane Anchoring in Cells.” The Journal of Cell Biology 222, no. 3 (March 6, 2023): e202203016. https://doi.org/10.1083/jcb.202203016.
PUBLICATIONS 2022
Héluain, Valentin, Grégoire Prévot, Bastien Cabarrou, Olivier Calvayrac, Estelle Taranchon-Clermont, Alain Didier, Sandrine Tabourier-Gouin, Julie Milia, and Julien Mazières. “Clinical and Molecular Analysis of Lung Cancers Associated with Fibrosing Interstitial Lung Disease.” Respiratory Medicine and Research 83 (November 30, 2022): 100946. https://doi.org/10.1016/j.resmer.2022.100946.
Carrier, Arnaud, Cécile Desjobert, Valérie Lobjois, Lise Rigal, Florence Busato, Jörg Tost, Miquel Ensenyat-Mendez, et al. “Epigenetically Regulated PCDHB15 Impairs Aggressiveness of Metastatic Melanoma Cells.” Clinical Epigenetics 14, no. 1 (November 28, 2022): 156. https://doi.org/10.1186/s13148-022-01364-x.
Pérez-García, José Manuel, Geraldine Gebhart, Manuel Ruiz Borrego, Peter Schmid, Frederik Marmé, Aleix Prat, Florence Dalenc, et al. “Trastuzumab and Pertuzumab without Chemotherapy in Early-Stage HER2+ Breast Cancer: A Plain Language Summary of the PHERGain Study.” Future Oncology (London, England), October 27, 2022. https://doi.org/10.2217/fon-2022-0663.
Bidard, François-Clément, Anne-Claire Hardy-Bessard, Florence Dalenc, Thomas Bachelot, Jean-Yves Pierga, Thibault de la Motte Rouge, Renaud Sabatier, et al. “Switch to Fulvestrant and Palbociclib versus No Switch in Advanced Breast Cancer with Rising ESR1 Mutation during Aromatase Inhibitor and Palbociclib Therapy (PADA-1): A Randomised, Open-Label, Multicentre, Phase 3 Trial.” The Lancet. Oncology, September 29, 2022, S1470-2045(22)00555-1. https://doi.org/10.1016/S1470-2045(22)00555-1.
Carrier, Arnaud, Cécile Desjobert, Loic Ponger, Laurence Lamant, Matias Bustos, Jorge Torres-Ferreira, Rui Henrique, et al. “DNA Methylome Combined with Chromosome Cluster-Oriented Analysis Provides an Early Signature for Cutaneous Melanoma Aggressiveness.” ELife 11 (September 20, 2022): e78587. https://doi.org/10.7554/eLife.78587.
Keller, Laura, Claudine Tardy, Laetitia Ligat, Soazig Le Pennec, Nicolas Bery, Faten Koraïchi, Patrick Chinestra, et al. “Tripartite Split-GFP Assay to Identify Selective Intracellular Nanobody That Suppresses GTPase RHOA Subfamily Downstream Signaling.” Frontiers in Immunology 13 (August 18, 2022): 980539. https://doi.org/10.3389/fimmu.2022.980539.
Delahaye, Celia, Sarah Figarol, Anne Pradines, Gilles Favre, Julien Mazieres, and Olivier Calvayrac. “Early Steps of Resistance to Targeted Therapies in Non-Small-Cell Lung Cancer.” Cancers 14, no. 11 (May 25, 2022): 2613. https://doi.org/10.3390/cancers14112613.
Callens, Celine, Francois-Clement Bidard, Anaïs Curto-Taribo, Olfa Trabelsi-Grati, Samia Melaabi, Suzette Delaloge, Anne-Claire Hardy-Bessard, et al. “Real-Time Detection of ESR1 Mutation in Blood by Droplet Digital PCR in the PADA-1 Trial: Feasibility and Cross-Validation with NGS.” Analytical Chemistry 94, no. 16 (April 26, 2022): 6297–6303. https://doi.org/10.1021/acs.analchem.2c00446.
Martins, Carla Silva, Cyntia Taveneau, Gerard Castro-Linares, Mikhail Baibakov, Nicolas Buzhinsky, Mar Eroles, Violeta Milanović, et al. “Human Septins in Cells Organize as Octamer-Based Filaments Mediating Actin-Membrane Anchoring.” Preprint. Cell Biology, February 24, 2022. https://doi.org/10.1101/2022.02.23.481653.
PUBLICATIONS 2021
Solomon, Benjamin J., Todd M. Bauer, Filippo de Marinis, Enriqueta Felip, Yasushi Goto, Geoffrey Liu, Julien Mazieres, et al. “Plain Language Summary of the CROWN Study Comparing Lorlatinib with Crizotinib for People with Untreated Non-Small Cell Lung Cancer.” Future Oncology (London, England) 17, no. 34 (December 1, 2021): 4649–56. https://doi.org/10.2217/fon-2021-0904.
Le, Xiuning, Hiroshi Sakai, Enriqueta Felip, Remi Veillon, Marina Chiara Garassino, Jo Raskin, Alexis B. Cortot, et al. “Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice.” Clinical Cancer Research, November 17, 2021, 1078-0432.CCR-21–2733. https://doi.org/10.1158/1078-0432.CCR-21-2733.
Ramalingam, Suresh S., Silvia Novello, Salih Zeki Guclu, Dmitry Bentsion, Zanete Zvirbule, Maria Szilasi, Reyes Bernabe, et al. “Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 39, no. 32 (November 10, 2021): 3633–44. https://doi.org/10.1200/JCO.20.03318.
Keller, Laura, Claudine Tardy, Laetitia Ligat, Julia Gilhodes, Thomas Filleron, Nicolas Bery, Philippe Rochaix, et al. “Nanobody-Based Quantification of GTP-Bound RHO Conformation Reveals RHOA and RHOC Activation Independent from Their Total Expression in Breast Cancer.” Analytical Chemistry 93, no. 15 (April 20, 2021): 6104–11. https://doi.org/10.1021/acs.analchem.0c05137.
Klionsky, Daniel J., Amal Kamal Abdel-Aziz, Sara Abdelfatah, Mahmoud Abdellatif, Asghar Abdoli, Steffen Abel, Hagai Abeliovich, et al. “Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (4th Edition)1.” Autophagy 17, no. 1 (January 2021): 1–382. https://doi.org/10.1080/15548627.2020.1797280.
Bery, Nicolas, Gilles Favre, and Aurélien Olichon. “Protocol to Select Conformation-Specific Intracellular Antibodies for Targeted Protein Degradation in an Engineered Cell Line.” STAR Protocols 2, no. 1 (2021): 100249. https://doi.org/10.1016/j.xpro.2020.100249.
Cristini, Agnese, Mathéa Géraud, and Olivier Sordet. “Transcription-Associated DNA Breaks and Cancer: A Matter of DNA Topology.” International Review of Cell and Molecular Biology 364 (2021): 195–240. https://doi.org/10.1016/bs.ircmb.2021.05.001.
PUBLICATIONS 2020
Durin, Lucile, Anne Pradines, Céline Basset, Bryan Ulrich, Laura Keller, Vincent Dongay, Gilles Favre, Julien Mazieres, and Nicolas Guibert. “Liquid Biopsy of Non-Plasma Body Fluids in Non-Small Cell Lung Cancer: Look Closer to the Tumor!” Cells 9, no. 11 (November 16, 2020). https://doi.org/10.3390/cells9112486.
Laplagne, Chloé, Sarah Meddour, Sarah Figarol, Marie Michelas, Olivier Calvayrac, Gilles Favre, Camille Laurent, Jean-Jacques Fournié, Stéphanie Cabantous, and Mary Poupot. “Vγ9Vδ2 T Cells Activation Through Phosphoantigens Can Be Impaired by a RHOB Rerouting in Lung Cancer.” Frontiers in Immunology 11 (July 7, 2020): 1396. https://doi.org/10.3389/fimmu.2020.01396.
Guibert, Nicolas, Anne Pradines, Gilles Favre, and Julien Mazieres. “Current and Future Applications of Liquid Biopsy in Nonsmall Cell Lung Cancer from Early to Advanced Stages.” European Respiratory Review: An Official Journal of the European Respiratory Society 29, no. 155 (March 31, 2020). https://doi.org/10.1183/16000617.0052-2019.
Cristini, Agnese, Natalia Gromak, and Olivier Sordet. “Transcription-Dependent DNA Double-Strand Breaks and Human Disease.” Molecular & Cellular Oncology 7, no. 2 (March 3, 2020): 1691905. https://doi.org/10.1080/23723556.2019.1691905.
Guibert, Nicolas, Anne Pradines, Gilles Favre, and Julien Mazières. “La Recherche de Mutations Dans l’ADN Tumoral Circulant Aide à Prédire La Réponse à l’immunothérapie Dans Le Cancer Du Poumon.” Médecine/Sciences 36, no. 5 (2020): 437–39. https://doi.org/10.1051/medsci/2020068.
PUBLICATIONS 2019
Bousquet Mur, Emilie, Sara Bernardo, Laura Papon, Maicol Mancini, Eric Fabbrizio, Marion Goussard, Irene Ferrer, et al. “Notch Inhibition Overcomes Resistance to Tyrosine Kinase Inhibitors in EGFR-Driven Lung Adenocarcinoma.” The Journal of Clinical Investigation, October 31, 2019. https://doi.org/10.1172/JCI126896.
Cristini, Agnese, Giulia Ricci, Sébastien Britton, Simona Salimbeni, Shar-Yin Naomi Huang, Jessica Marinello, Patrick Calsou, et al. “Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks.” Cell Reports 28, no. 12 (September 17, 2019): 3167-3181.e6. https://doi.org/10.1016/j.celrep.2019.08.041.
Bery, Nicolas, Laura Keller, Marjorie Soulié, Rémi Gence, Anne-Laure Iscache, Julia Cherier, Stéphanie Cabantous, et al. “A Targeted Protein Degradation Cell-Based Screening for Nanobodies Selective toward the Cellular RHOB GTP-Bound Conformation.” Cell Chemical Biology, September 11, 2019. https://doi.org/10.1016/j.chembiol.2019.08.009.
Guibert, Nicolas, Greg Jones, John F. Beeler, Vincent Plagnol, Clive Morris, Jean Mourlanette, Myriam Delaunay, et al. “Targeted Sequencing of Plasma Cell-Free DNA to Predict Response to PD1 Inhibitors in Advanced Non-Small Cell Lung Cancer.” Lung Cancer (Amsterdam, Netherlands) 137 (September 6, 2019): 1–6. https://doi.org/10.1016/j.lungcan.2019.09.005.
Mouly, Laetitia, Julia Gilhodes, Anthony Lemarié, Elizabeth Cohen-Jonathan Moyal, Christine Toulas, Gilles Favre, Olivier Sordet, and Sylvie Monferran. “The RND1 Small GTPase: Main Functions and Emerging Role in Oncogenesis.” International Journal of Molecular Sciences 20, no. 15 (July 24, 2019). https://doi.org/10.3390/ijms20153612.
Tichauer, Ruth H., Gilles Favre, Stéphanie Cabantous, and Marie Brut. “Hybrid QM/MM vs Pure MM Molecular Dynamics for Evaluating Water Distribution within P21N-Ras and the Resulting GTP Electronic Density.” The Journal of Physical Chemistry. B 123, no. 18 (May 9, 2019): 3935–44. https://doi.org/10.1021/acs.jpcb.9b02660.
Keller, Laura, Nicolas Guibert, Anne Casanova, Stephanie Brayer, Magali Farella, Myriam Delaunay, Julia Gilhodes, et al. “Early Circulating Tumour DNA Variations Predict Tumour Response in Melanoma Patients Treated with Immunotherapy.” Acta Dermato-Venereologica 99, no. 2 (February 1, 2019): 206–10. https://doi.org/10.2340/00015555-3080.
Desjobert, Cécile, Arnaud Carrier, Audrey Delmas, Diego M. Marzese, Antoine Daunay, Florence Busato, Arnaud Pillon, et al. “Demethylation by Low-Dose 5-Aza-2’-Deoxycytidine Impairs 3D Melanoma Invasion Partially through MiR-199a-3p Expression Revealing the Role of This MiR in Melanoma.” Clinical Epigenetics 11, no. 1 (January 16, 2019): 9. https://doi.org/10.1186/s13148-018-0600-2.
De Magis, Alessio, Stefano G. Manzo, Marco Russo, Jessica Marinello, Rita Morigi, Olivier Sordet, and Giovanni Capranico. “DNA Damage and Genome Instability by G-Quadruplex Ligands Are Mediated by R Loops in Human Cancer Cells.” Proceedings of the National Academy of Sciences of the United States of America 116, no. 3 (January 15, 2019): 816–25. https://doi.org/10.1073/pnas.1810409116.
Keller, Laura, Nicolas Bery, Claudine Tardy, Laetitia Ligat, Gilles Favre, Terence H. Rabbitts, and Aurélien Olichon. “Selection and Characterization of a Nanobody Biosensor of GTP-Bound RHO Activities.” Antibodies (Basel, Switzerland) 8, no. 1 (January 9, 2019). https://doi.org/10.3390/antib8010008.
Calvayrac, Olivier, Ada Nowosad, Stéphanie Cabantous, Lin-Po Lin, Sarah Figarol, Pauline Jeannot, Murielle P. Serres, et al. “Cytoplasmic P27Kip1 Promotes Tumorigenesis via Suppression of RhoB Activity.” The Journal of Pathology 247, no. 1 (January 2019): 60–71. https://doi.org/10.1002/path.5167.
TEAM MEMBERS
PARTNERSHIPS & FUNDING
Centre de Recherches en Cancérologie de Toulouse (Oncopole)
Toulouse – FR
New study out from the lab on the preclinical characterization of #GeneTherapy for patients with #PancreaticCancer . Thanks to @CHUdeToulouse and @invivogen_US for the wonderful collaboration
https://www.sciencedirect.com/science/article/pii/S2329050123000414
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05 82 74 15 75
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L’équipe du CRCT ?
L’équipe du CRCT ?
