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

THE TEAM’S
FOCUS

Discover

Prevention of resistances to targeted therapies in lung cancer with a new therapeutic combination.

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TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks

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Focus research 2022 SIGNATHER team

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The level of von Willebrand factor is a pronostic marker in patients with metastatic melanoma treated by immune checkpoint inhibitors

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Fighting bronchial cancers

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Understand

On the occasion of the World Cancer Day, digital round table “Toulouse: innovation in oncology (in french)

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Participate

TOW2025 J-30 Earlybird registration

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12th Summer School on Medicines

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Live

Favre/Sordet team Follow 15 49

Our research focuses on the signaling pathways and molecular mechanisms driving cancer progression and therapeutic resistance

SIGNATHER
Voir plus

SCIENTIFIC PRODUCTIONS

PUBLICATIONS 2024
Lévrier, Antoine, Julien Capin, Pauline Mayonove, Ioannis-Ilie Karpathakis, Peter Voyvodic, Angelique DeVisch, Ana Zuniga, et al. “Split Reporters Facilitate Monitoring of Gene Expression and Peptide Production in Linear Cell-Free Transcription-Translation Systems.” ACS Synthetic Biology, September 18, 2024. https://doi.org/10.1021/acssynbio.4c00353.
Sementsov, Mark, Leonie Ott, Julian Kött, Alexander Sartori, Amelie Lusque, Sarah Degenhardt, Bertille Segier, et al. “Mutation Analysis in Individual Circulating Tumor Cells Depicts Intratumor Heterogeneity in Melanoma.” EMBO Molecular Medicine 16, no. 7 (July 2024): 1560–78. https://doi.org/10.1038/s44321-024-00082-6.
Figarol, Sarah, Célia Delahaye, Rémi Gence, Aurélia Doussine, Juan Pablo Cerapio, Mathylda Brachais, Claudine Tardy, et al. “Farnesyltransferase Inhibition Overcomes Oncogene-Addicted Non-Small Cell Lung Cancer Adaptive Resistance to Targeted Therapies.” Nature Communications 15, no. 1 (June 27, 2024): 5345. https://doi.org/10.1038/s41467-024-49360-4.
Toublanc, Anne-Claire, Maxime Faure, Guillaume Verdy, Audrey Rabeau, Valérie Houard, Rémi Veillon, Claire Bardel, et al. “Prospective Cardiovascular Events in Patients with Advanced Thoracic Cancer Treated with Immune Checkpoint Inhibitor.” European Journal of Cancer (Oxford, England: 1990) 207 (June 24, 2024): 114191. https://doi.org/10.1016/j.ejca.2024.114191.
Geraud, Mathéa, Agnese Cristini, Simona Salimbeni, Nicolas Bery, Virginie Jouffret, Marco Russo, Andrea Carla Ajello, et al. “TDP1 Mutation Causing SCAN1 Neurodegenerative Syndrome Hampers the Repair of Transcriptional DNA Double-Strand Breaks.” Cell Reports 43, no. 5 (May 16, 2024): 114214. https://doi.org/10.1016/j.celrep.2024.114214.
Duarte-Silva, Sara, Jorge Diogo Da Silva, Daniela Monteiro-Fernandes, Marta Daniela Costa, Andreia Neves-Carvalho, Mafalda Raposo, Carina Soares-Cunha, et al. “Glucocorticoid Receptor-Dependent Therapeutic Efficacy of Tauroursodeoxycholic Acid in Preclinical Models of Spinocerebellar Ataxia Type 3.” The Journal of Clinical Investigation 134, no. 5 (March 1, 2024): e162246. https://doi.org/10.1172/JCI162246.
PUBLICATIONS 2023
Polge, Cécile, Stéphanie Cabantous, and Daniel Taillandier. “Tripartite Split-GFP for High Throughput Screening of Small Molecules: A Powerful Strategy for Targeting Transient/Labile Interactors like E2-E3 Ubiquitination Enzymes.” Chembiochem: A European Journal of Chemical Biology, December 13, 2023, e202300723. https://doi.org/10.1002/cbic.202300723.
Castillo, Sebastian, Rémi Gence, Delphine Pagan, Faten Koraïchi, Catherine Bouchenot, Benoit J. Pons, Betty Boëlle, et al. “Visualizing the Subcellular Localization of RHOB-GTP and GTPase-Effector Complexes Using a Split-GFP/Nanobody Labelling Assay.” European Journal of Cell Biology 102, no. 4 (August 21, 2023): 151355. https://doi.org/10.1016/j.ejcb.2023.151355.
Boutonnet, Audrey, Anne Pradines, Marion Mano, Marion Kreczman-Brun, Julien Mazières, Gilles Favre, and Frédéric Ginot. “Size and Concentration of Cell-Free DNA Measured Directly from Blood Plasma, without Prior DNA Extraction.” Analytical Chemistry 95, no. 24 (June 20, 2023): 9263–70. https://doi.org/10.1021/acs.analchem.3c00998.
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 (June 2023): 100946. https://doi.org/10.1016/j.resmer.2022.100946.
Mascarau, Rémi, Marie Woottum, Léa Fromont, Rémi Gence, Vincent Cantaloube-Ferrieu, Zoï Vahlas, Kevin Lévêque, et al. “Productive HIV-1 Infection of Tissue Macrophages by Fusion with Infected CD4+ T Cells.” The Journal of Cell Biology 222, no. 5 (May 1, 2023): e202205103. https://doi.org/10.1083/jcb.202205103.
Stadler, Julia-Christina, Laura Keller, Christian Mess, Alexander T. Bauer, Julian Koett, Glenn Geidel, Isabel Heidrich, et al. “Prognostic Value of von Willebrand Factor Levels in Patients with Metastatic Melanoma Treated by Immune Checkpoint Inhibitors.” Journal for Immunotherapy of Cancer 11, no. 5 (May 2023): e006456. https://doi.org/10.1136/jitc-2022-006456.
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
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.
Cristini, Agnese, Michael Tellier, Flavia Constantinescu, Clelia Accalai, Laura Oana Albulescu, Robin Heiringhoff, Nicolas Bery, Olivier Sordet, Shona Murphy, and Natalia Gromak. “RNase H2, Mutated in Aicardi-Goutières Syndrome, Resolves Co-Transcriptional R-Loops to Prevent DNA Breaks and Inflammation.” Nature Communications 13, no. 1 (May 26, 2022): 2961. https://doi.org/10.1038/s41467-022-30604-0.
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

Maïna Vienne
Ingénieur de laboratoire / laboratory engineer
Célia Delahaye
Chercheur Post-Doctorant / Post-Doc researcher
Eglantine Faget
Master / Master student
Béatrice Cena
Ingénieur de laboratoire / laboratory engineer
Manon Boulet
Ingénieur de laboratoire / laboratory engineer
Carl KHAWLY
Doctorant / PhD student
Aurélia Doussine
Ingénieur de laboratoire / laboratory engineer
Andrea Carla Ajello
Doctorant / PhD student
Julien Mazières
Hospitalo-Universitaire / University teacher hospital practitioner
Mathéa Géraud
Doctorant / PhD student
Gilles Favre
Hospitalo-Universitaire / University teacher hospital practitioner
Laura Keller
Enseignant chercheur / University researcher
Agnese Cristini
Chercheur statutaire / permanent scientist
Sebastian Castillo
Doctorant / PhD student
Lara Fernandez-Martinez
Doctorant / PhD student
Delphine Pagan
Ingénieur de laboratoire / laboratory engineer
Anne Pradines
Chercheur statutaire / permanent scientist
Estelle Clermont
Ingénieur de laboratoire / laboratory engineer
Stephanie Cabantous
Chercheur statutaire / permanent scientist
Olivier Calvayrac
Chercheur statutaire / permanent scientist
12

PARTNERSHIPS & FUNDING

Centre de Recherches en Cancérologie de Toulouse
Centre de Recherches en Cancérologie de Toulouse (Oncopole)
Toulouse – FR
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