In vivo platform of Canceropole Grand Ouest

Team description

Our team is dedicated to the in vivo evaluation of a variety of compounds in pre-clinical animal models. We have a whole collection of murine and human cancer cell lines with well-documeted mutational status, used to assess the efficacy of these compounds in term of tumor growth control. In addition, since the channel blockade may interfere with cell migration and the expression of the metastatic phenotype, Luciferase positive cell lines will also be used to evaluate metastatic spreading inhibition by repeated Bioluminescence imaging over time in well-defined pre-clinical model relevant to the natural history of such tumors in human beings.

Role in the network

The cell lines to be used in pre-clinical growth inhibition trials will be selected for in vivo assessment based on data generated by UMR1069 team, including MDA-MB-435s breast cancer and others having shown in vitro sensitivity the SK3 channel blockers.

In addition, since the channel blockade may interfere with cell migration and the expression of the metastatic phenotype, Luciferase positive cell lines will also be used to evaluate metastatic spreading inhibition by repeated Biolumiescence imaging over time in well-defined pre-clinical model relevant to the natural history of such tumors in human beings.
Channels Inhibitors (Orai/STIM, TRPC 1,4 and SK3) selected on the in vitro ImpactCell platform will be tested in vivo in preclinical models of nude mice xenografted with tumours of interest (Breast, prostate, colon adenocarcinoma for both tolerance/toxicity and tumor progression inhibition. Finally, potential reversal of resistance to chemotherapy or targeted agents by the concurrent use of channel inhibitors will be evaluated.

Involvement in tasks 6

 In vivo evaluation in pre-clinical models.

Valorizations/Collaborations

Publications / Patents

Driffort V, Gillet L, Bon E, Marionneau-Lambot S, Oullier T, Joulin V, Collin C, Pagès JC, Jourdan ML, Chevalier S, Bougnoux P, Le Guennec JY, Besson P, Roger S. Ranolazineinhibits NaV1.5-mediated breast cancer cellinvasiveness and lungcolonization. Mol Cancer. 2014 Dec 11;13(1):264.

PRIMA-1Met induces myeloma cell death independent of p53 by impairing the GSH/ROS balance. Tessoulin B, Descamps G, Moreau P, Maïga S, Lodé L, Godon C, Marionneau-Lambot S, Oullier T, Le Gouill S, Amiot M, Pellat-Deceunynck C. Blood. 2014 Sep 4;124(10):1626-36.

Improved Functionality of the Vasculature during Conventionally Fractionated Radiation Therapy of Prostate Cancer. Potiron VA, Abderrahmani R, Clément-Colmou K, Marionneau-Lambot S, Oullier T, Paris F, Supiot S. PLoS One. 2013 Dec 31;8(12):e84076

Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts. Boulahjar R, Ouach A, Matteo C, Bourg S, Ravache M, le Guével R, Marionneau S, Oullier T, Lozach O, Meijer L, Guguen-Guillouzo C, Lazar S, Akssira M, Troin Y, Guillaumet G, Routier S. J Med Chem. 2012 Nov 26;55(22):9589-606.

Critical role of the NOTCH ligand JAG2 in self-renewal of myeloma cells. David Chiron, Sophie Maïga, Régis Bataille, Jérôme Moreaux, Bernard Klein, Philippe Moreau, Jean-Luc Harousseau, Martine Amiot, Séverine Marionneau Lambot, Thibauld Oullier, Catherine Pellat-Deceunynck. Blood Cells Mol Dis. 2012 Feb 15.

3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice. Hunault, J.; Diswall, M.; Frison, J.-C. Blot, V.; Rocher, J.; Marionneau-Lambot, S.; Oullier, T.; Douillard, J.-Y.; Guillarme, S.; Saluzzo, C.; Dujardin, G.; Jacquemin, D.; Graton, J.; Le Questel, J.Y.; Evain, M.; Lebreton, J.; Dubreuil, D.; Le Pendu, J.; Pipelier, M. J. Med. Chem. 2012, 55, 1227−1241

A phase II, open-label, randomized study to assess the efficacy and safety if the MEK1/2 inhibitor AZD6244 B(ARRY-142886) versus capectabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapy regimens. J Bennouna, I Lang, M Valladeres-Ayerbes, K Boer, A Adenis, P Escudero, T Y Kim, GM Pover, CD Morris, JY Douillard. Invest New Drug 2011, 29(5); 1021-1028.

A phase I dose-escalation study of edotecarin (J-107088) combined with infusional 5-fluorouracil and leucovorin in patients with advanced/metastatic solid tumors. Saif MW, Sellers S, Diasio RB, Douillard JY. Anticancer Drugs 2010, 21(7); 716-23.

Randomized phase III trial of Panitumumab with infusionalFluoroUracil, Leucovorin and Oxaliplatin (FOLFOX 4) versus FOLFOX 4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem R, Rivera F, Kocakoca I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. J. Clin. Oncol. 2010; 28 (31); 4697-705.

Focus on the controversial activation of human iNKT cells by 4-deoxy analogue of KRN7000. Lacône V, Hunault J, Pipelier M, Blot V, Lecourt T, Rocher J, Turcot-Dubois AL, Marionneau S, Douillard JY, Clément M, Le Pendu J, Bonneville M, Micouin L, Dubreuil D. J Med Chem. 2009; 52(15):4960-3.

Meriolins, a new class of cell death-inducing kinase inhibitors with inhibitors with enhanced selectivity for cyclin-dependent kinases. Bettayeb, K., Tirado, O.M., Marionneau-Lambot, S., Ferandin, Y., Lozach, O., Morris, J.C., Mateo-Lozano, S., Drueckes, P., Schächtele, C., Kubbutat, M., Liger, F., Marquet, B., Joseph, B., Echalier, A., Endicott, J., Notario, V. and Meijer, L. Cancer Res, 2007 67, 8325-8334.

Linked to network

Pivotal role of the lipid Raft SK3-Orai1 complex in human cancer cell migration and bone metastases. Chantôme A, Potier-Cartereau M, Clarysse L, Fromont G, Marionneau-Lambot S, Guéguinou M, Pagès JC, Collin C, Oullier T, Girault A, Arbion F, Haelters JP, Jaffrès PA, Pinault M, Besson P, Joulin V, Bougnoux P, Vandier C. Cancer Res. 2013 Aug 1;73(15):4852-61.

Inhibition of SK3/KCa2.3 channel by 1-O-hexadecyl-2-O-methyl-sn-glycero-3-lactose reduces cell migration and metastasis development. Girault A, HaeltersJ.P, PotierM, ChantômeA, PinaultM., Marionneau-Lambot S, Oullier T, Simon Couthon-Gourvès H, Jaffrès P.A, Corbel B, Bougnou P, Joulin V, Vandier C. Curr Cancer Drug Targets. 2011 Nov 1