Accueil > Research Teams > Oncopharmacology
Oncopharmacology
Objectives
In our group, we study interactions between cancer drugs and tumor cells, and we propose new therapeutic approaches based on the knowledge of these interactions. We study different treatments (small molecules, monoclonal antibodies, antibody-drug conjugates, immunomodulators…) on different models of cell culture, co-culture, cell printing or animal models, representing both hematologic malignancies and solid tumors.
Projects
Anticancer drugs are part of the tumor microenvironment of cancer patients as long as they are treated with small-molecule- or monoclonal antibody-based chemotherapy. We are interested in interactions between these drugs and the cancer cells within the tumor, but also with cells of the microenvironment (immune cells, fibroblasts, adipocytes…). Our studies concern mechanisms of action and resistance of the drugs, their action on cells and the action of cells on the drugs, as well as the development of new therapeutic strategies based on the obtained knowledge. A second aspect of our research concerns the study of the role of certain proteins in the biology of cancer cells. We are here interested in proteins identified in the work on drugs and treatments. We use an approach that includes studies on cell models, animal models, clinical samples and patients. Our team is composed of researchers, university lecturers and hospital practitioners together with a solid technical staff and students. We have collaborators in the field of chemistry, molecular modelling, biology and industrial partners, allowing us to be actors of therapeutic innovation. We also have strong links to the clinics for translational research and study of prognostic factors. Several biotech companies have been created over the last years with a strong implication of our team and on the basis of research within our team.
We do not limit our work to one specific tumor or one specific treatment, but apply our scientific approach to various projects. Here are some examples:
- Study of resistance to anti-PD1/PD-L1 antibodies on syngeneic models of in vivo This project allows to characterize the resistance with its modification of cancer cells and immune infiltrations, and to propose new approaches allowing to regain activity on resistant models.
- Role of physical constraints in the development of pancreatic cancer, and implication on treatments.
- The use of cellular 3D printing to create relevant models with several cell types for the study of anticancer drug activity.
- Inhibition of DNA repair with protein-protein interaction inhibitors to increase the activity of certain anticancer treatments.
- Role of genetic translocations of the response of lung cancer to targeted therapies.
- Development of inhibitors of 5’-nucleotidases and study of the role of proteins in the nucleotide metabolism in the biology of cancer cells.
- Stimulation of the immune system by formulated LPS or G-CSF in preclinical and clinical studies.
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Charles DUMONTET
charles.dumontet@chu-lyon.fr
04 78 77 71 23Lars Petter JORDHEIM
lars-petter.jordheim@univ-lyon1.frFaculté Rockefeller
4ème étage, escalier D
8 avenue Rockefeller
69008 Lyon
Members
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GROSJEAN Clémence
Ingénieure d'étude - Eq C Dumontet / LP Jordheim
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CADIOU Aurélie
Doctorante CIFRE - Equipe C Dumotet / LP Jordheim
Main financing
ANR Blanc
INCa Projets libres
ARC
Ligue Nationale Contre le Cancer
CLARA – Preuve de Concept
Publications
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SLX4 and XPF are involved in cell migration and EMT in a cell-specific manner.
Cros-Perrial E, Beaumel S, Gimbert M, Camus N, Vicente C, Sekiou I, Figuet L, Duruisseaux M, Dumontet C, Jordheim LP. Biochemical Pharmacology
A phenotypic journey into NT5DC proteins in cancer and other diseases.Cros-Perrial E, Jordheim LP. Experimental cell research
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The synergy between alkylating agents and ERCC1-XPF inhibitors is p53 dependent.
Ciniero G, Pedro TM, Dumontet C, Elmenoufy AH, West FG, Weinfeld M, Gentile F, Tuszynski JA, Cros-Perrial E, Jordheim LP. Fundamental and clinical pharmacology
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A systemically administered detoxified TLR4 agonist displays potent antitumor activity and an acceptable tolerance profile in preclinical models.
Chettab K, Fitzsimmons C, Novikov A, Denis M, Phelip C, Mathé D, Choffour PA, Beaumel S, Fourmaux E, Norca P, Kryza D, Evesque A, Jordheim LP, Perrial E, Matera EL, Caroff M, Kerzerho J, Dumontet C. Frontiers in immunology
OXPHOS inhibitors, metabolism and targeted therapies in cancer.Cadassou O, Jordheim LP. Biochemical pharmacology
Payload diversification: a key step in the development of antibody-drug conjugates.Conilh L, Sadilkova L, Viricel W, Dumontet C. Journal of hematology and oncology
Impact of mouse model tumor implantation site on acquired resistance to anti-PD-1 immune checkpoint therapy.Denis M, Mathé D, Micoud M, Choffour PA, Grasselly C, Matera EL, Dumontet C. Frontiers in immunology
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In vivo syngeneic tumor models with acquired resistance to anti-PD-1/PD-L1 therapies.
Denis M, Grasselly C, Choffour PA, Wierinckx A, Mathe D, Chettab K, Tourette A, Talhi N, Bourguignon A, Birzele F, Kress E, Jordheim LP, Klein C, Matera EL, Dumontet C.
Proof of Concept: Protein Delivery into Human Erythrocytes Using Stable Cavitation
Cancer Immunology ResearchChettab K, Matera EL, Lafond M, Coralie D, Favin-Lévêque C, Goy C, Strakhova R, Mestas JL, Lafon C, Dumontet C Molecular Pharmaceutics
Prognostic impact of cN-III mRNA expression on overall survival and drug sensitivity in pediatric leukemiaDomenech C, Plesa A, Tourette A, Bertrand Y, Dony A, Dumontet C, Cros-Perrial E, Jordheim LP Leukemia & Lymphoma
Netrin-1 expression and targeting in multiple myelomaFahed D, Chettab A, Mathe D, Denis M, Traverse-Glehen A, Karlin L, Perrial E, Dumontet C Leukemia & Lymphoma
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Loss of KDM1A in GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing’s syndrome: a multicentre, retrospective, cohort study
Chasseloup F, Bourdeau I, Tabarin A, Regazzo D, Dumontet C, Ladurelle N, Tosca L, Amazit L, Proust A, Scharfmann R, Mignot T, Fiore F, Tsagarakis S, Vassiliadi D, Maiter D, Young J, Lecoq AL, Deméocq V, Salenave S, Lefebvre H, Cloix L, Emy P, Dessailloud R, Vezzosi D, Scaroni C, Barbot M, de Herder W, Pattou F, Tétreault M, Corbeil G, Dupeux M, Lambert B, Tachdjian G, Guiochon-Mantel A, Beau I, Chanson P, Viengchareun S, Lacroix A, Bouligand J, Kamenický P The Lancet Diabetes & Endocrinology
Transcriptional and Metabolic Investigation in 5′-Nucleotidase Deficient Cancer Cell LinesCadassou, O.; Forey, P.; Machon, C.; Petrotto, E.; Chettab, K.; Tozzi, M.G.; Guitton, J.; Dumontet, C.; Cros-Perrial, E.; Jordheim, L.P. Cells
CD73 and cN-II regulate the cellular response to chemotherapeutic and hypoxic stress in lung adenocarcinoma cellsRaza MZ, Cadassou O, Dumontet C, Cros-Perrial E & Jordheim LP Biochimica et Biophysica Acta – General Subjects
Exatecan antibody drug conjugates based on a hydrophilic polysarcosine drug-linker platformConilh L, Fournet G, Fourmaux E, Murcia A, Matera EL, Joseph B, Dumontet C & Viricel W Pharmaceutical
Enhancing the activity of platinum-based drugs by improved inhibition of ERCC1-XPF mediated DNA repairCiniero G, Elmenoufy AH, Gentile F, Weinfeld M, Deriu MA, West FG, Tuszynski JA, Dumontet C, Cros-Perrial E & Jordheim LP Cancer Chemotherapy and Pharmacology
Enhanced migration of breast and lung cancer cells deficient for cN-II and CD73 via COX-2/PGE2/Akt axis regulationCadassou O, Raza MZ, Machon C, Gudefin L, Armanet C, Chettab K, Guitton J, Tozzi MG, Dumontet C, Cros-Perrial E & Jordheim LP Cellular Oncology
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Calcium channel blockers impair the antitumor activity of anti-CD20 monoclonal antibodies by blocking EGR-1 induction
Spasevska I, Chettab K, Matera EL, Ville J, Potier-Cartereau M, Jordheim LP, Thieblemont C, Sahin D, Klein C & Dumontet C Molecular Cancer Therapeutics
Adipocyte-conditioned medium induces resistance of breast cancer cells to lapatinibGeneste A, Duong MN, Molina L, Conilh L, Beaumel S, Cleret A, Chettab K, Lachat M, Jordheim LP, Matera EL & Dumontet C BMC Pharmacology and Toxicology
How Can Immune Checkpoint Inhibitors Cause Hyperprogression in Solid Tumors?Denis M, Duruisseaux M, Brevet M, Dumontet C Frontiers in Immunology
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Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma
Pertesi M, Vallee M, Wei X, Revuelta MV, Galia P, Demangel D, Oliver J, Foll M, Chen S, Perrial E, Garderet L, Corre J, Leleu X, Boyle EM, Decaux O, Rodon P, Kolb B, Slama B, Mineur P, Voog E, Le Bris C, Fontan J, Maigre M, Beaumont M, Azais I, Sobol H, Vignon M, Royer B, Perrot A, Fuzibet JG, Dorvaux V, Anglaret B, Cony-Makhoul P, Berthou C, Desquesnes F, Pegourie B, Leyvraz S, Mosser L, Frenkiel N, Augeul-Meunier K, Leduc I, Leyronnas C, Voillat L, Casassus P, Mathiot C, Cheron N, Paubelle E, Moreau P, Bignon YJ, Joly B, Bourquard P, Caillot D, Naman H, Rigaudeau S, Marit G, Macro M, Lambrecht I, Cliquennois M, Vincent L, Helias P, Avet-Loiseau H, Moreno V, Reis RM, Varkonyi J, Kruszewski M, Vangsted AJ, Jurczyszyn A, Zaucha JM, Sainz J, Krawczyk-Kulis M, Watek M, Pelosini M, Iskierka-Jazdzewska E, Grzasko N, Martinez-Lopez J, Jerez A, Campa D, Buda G, Lesueur F, Dudzinski M, Garcia-Sanz R, Nagler A, Rymko M, Jamroziak K, Butrym A, Canzian F, Obazee O, Nilsson B, Klein RJ, Lipkin SM, McKay JD, Dumontet C Leukemia
Lead optimization and biological evaluation of fragment-based cN-II inhibitorsGuillon R, Rahimova R, Preeti, Egron D, Rouanet S, Dumontet C, Aghajari N, Jordheim LP, Chaloin L, Peyrottes S European Journal of Medicinal Chemistry
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The Antitumor Activity of Combinations of Cytotoxic Chemotherapy and Immune Checkpoint Inhibitors Is Model-Dependent
Grasselly C, Denis M, Bourguignon A, Talhi N, Mathe D, Tourette A, Serre L, Jordheim LP, Matera EL, Dumontet C Frontiers in Immunology
CD73 inhibition by purine cytotoxic nucleoside analogue-based diphosphonatesDumontet C, Peyrottes S, Rabeson C, Cros-Perrial E, Geant PY, Chaloin L, Jordheim LP European Journal of Medicinal Chemistry
A predictive model for risk of early grade >/= 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trialDumontet C, Hulin C, Dimopoulos MA, Belch A, Dispenzieri A, Ludwig H, Rodon P, Van Droogenbroeck J, Qiu L, Cavo M, Van de Velde A, Lahuerta JJ, Allangba O, Lee JH, Boyle E, Perrot A, Moreau P, Manier S, Attal M, Roussel M, Mohty M, Mary JY, Civet A, Costa B, Tinel A, Gaston-Mathe Y, Facon T Leukemia
Esophageal cancer cells resistant to T-DM1 display alterations in cell adhesion and the prostaglandin pathwaySauveur J, Matera EL, Chettab K, Valet P, Guitton J, Savina A, Dumontet C Oncotarget
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Neutrophils protect lymphoma cells against cytotoxic and targeted therapies through CD11b/ICAM-1 binding
Hirz T, Matera EL, Chettab K, Jordheim LP, Mathé D, Evesque A, Esmenjaud J, Salles G & Dumontet C Oncotarget
The cytosolic 5’-nucleotidase cN-II lowers the adaptability to glucose deprivation in human breast cancer cellBricard G, Cadassou O, Cassagnes LE, Cros-Perrial E, Payen L, Puy JY, Lefevbre-Tournier I, Tozzi MG, Dumontet C & Jordheim LP Oncotarget
Doxorubicin Delivery into Tumor Cells by Stable Cavitation without Contrast AgentsChettab K, Mestas JL, Lafond M, Saadna DE, Lafon C, Dumontet C Molecular Pharmaceutics
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Pegfilgrastim enhances the antitumor effect of therapeutic monoclonal antibodies
Cornet S, Mathe D, Chettab K, Evesque A, Matera EL, Tredan O, Dumontet C Molecular Cancer Therapeutics
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The purine analog fludarabine acts as a cytosolic 5′-nucleotidase II inhibitor
Cividini F, Pesi R, Chaloin L, Allegrini S, Camici M, Cros-Perrial E, Dumontet C, Jordheim LP, Tozzi MG Biochem Pharmacol .
Spatial and Temporal Control of Cavitation Allows High In Vitro Transfection Efficiency in the Absence of Transfection Reagents or Contrast AgentsChettab K, Roux S, Mathe D, Cros-Perrial E, Lafond M, Lafon C, Dumontet C, Mestas JL PLoS One .
Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patientsZiv E, Dean E, Hu D, Martino A, Serie D, Curtin K, Campa D, Aftab B, Bracci P, Buda G, Zhao Y, Caswell-Jin J, Diasio R, Dumontet C, Dudzinski M, Fejerman L, Greenberg A, Huntsman S, Jamroziak K, Jurczyszyn A, Kumar S, Atanackovic D, Glenn M, Cannon-Albright LA, Jones B, Lee A, Marques H, Martin T, Martinez-Lopez J, Rajkumar V, Sainz J, Vangsted AJ, Watek M, Wolf J, Slager S, Camp NJ, Canzian F, Vachon C Nat Commun .
ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patientsTredan O, Menetrier-Caux C, Ray-Coquard I, Garin G, Cropet C, Verronese E, Bachelot T, Rebattu P, Heudel PE, Cassier P, Chabaud S, Croughs T, Dupont P, Cadore AC, Clapisson G, Delgado A, Bardin-dit-Courageot C, Rigal C, N'Kodia A, Gilles-Afchain L, Morre M, Perol D, Blay JY, Caux C Ann Oncol .
Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicityDuong MN, Cleret A, Matera EL, Chettab K, Mathe D, Valsesia-Wittmann S, Clemenceau B, Dumontet C
Blinatumomab: a new era of treatment for adult ALL?Thomas X Lancet Oncology
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Apoptotic induction by anti-CD20 antibodies in chronic lymphocytic leukemia: comparison of rituximab and obinutuzumab
Reslan L, Dalle S, Herveau S, Perrial E, Dumontet C. Leuk Lymphoma .
Expression of domains for protein-protein interaction of nucleotide excision repair proteins modifies cancer cell sensitivity to platinum derivatives and genomic stabilityJordheim LP, Cros-Perrial E, Matera EL, Bouledrak K, Dumontet C Exp Pharmacol Physiol