Centre de Recherche en Cancérologie de Marseille UMR 1068 Inserm, UMR 7258 CNRS. Contact: Pr. Jean-Paul Borg

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1 Centre de Recherche en Cancérologie de Marseille UMR 1068 Inserm, UMR 7258 CNRS Contact: Pr. Jean-Paul Borg

2 Organisation du CRCM CPER CRCM (8000 m people) CRCM CIML Campus Timone (100 m 2-5 people) Campus Luminy (2300 m 2-45 people) IBDML

3 Molecular basis of oncogenesis and dissemination Innovative therapeutic approaches Molecular Oncology Daniel Birnbaum Cell Polarity, Cell Signaling and Cancer Jean-Paul Borg Signalization, hematopoiesis and mechanisms of oncogenesis Patrice Dubreuil Tumor Cell Motility Ali Badache Adhesion Molecules in Tumour/Host Interaction Michel Aurrand-Lions PDZ scaffold proteins and phosphoinositides in cell signalling and oncogenesis Pascale Zimmermann Epigenetic control of normal and pathological hematopoiesis Estelle Duprez Tolerance of lesions in DNA Robert Fuchs Telomere and senescence Vincent Géli Mechanisms of DNA double strand break repair system: homologous recombination and NHEJ Mauro Modesti Control of structure-specific endonucleases and genome stability Pierre-Henri Gaillard Genome dynamics and Recombination Bertrand Llorente Immunity and cancer Daniel Olive Fundamental and therapeutic chemical biology Yves Collette/Xavier Morelli Antibody therapeutics and immunotargeting Daniel Baty Cell stress Juan Iovanna Computational biology and Drug design Pedro Ballester People: 250 Countries: 25

4 Du lit du patient au laboratoire Mécanismes de l oncogenèse et dissémination tumorale: signalisation et polarité cellulaire, interactions hôte-tumeur, instabilité génomique, réparation/réplication de l ADN, épigénétique, stress cellulaire Nouvelles cibles thérapeutiques et biomarqueurs pour améliorer la prise en charge des cancers du sein, pancréas et leucémies Essais cliniques innovants en lien avec les activités translationnelles et fondamentales du CRCM

5 From bench to bedside Cloning of FLT3 and VEGFR genes Bone marrow transplantation

6 Explorer le processus tumoral pour mieux le combattre

7 Relations entre la tumeur et son environnement

8 Understanding of cancer complexity.

9 and development of therapeutic strategies Diagnosis, prognosis PIK3CA BRAF KRAS APC TP53 NRAS Treatment

10 Chimiothérapies: anciens et nouveaux concepts Chimiothérapie conventionnelle Ciblage thérapeutique

11 Cancer: loss and gain of cell polarity Normal Loss of cell polarity Invasion and dissemination E-cadherin LKB1 PAR3 SCRIB WNT5A, ROR2 PTK7, VANGL1 FZD-2

12 Technologies and platforms - Cell imaging - Animal house and transgenesis - Preclinical platform (TrGET) - Flow cytometry and cell sorting - Bioinformatics, Biostatistics - Experimental histo-pathology - Genomics and sequencing - Cell culture - Datacentre IT and Scientific Computing - Department of Clinical Research and Development - Data management and analysis center - Biotherapy and Cell therapy - Early Phase Trial center (ETOH) - Nanobodies - Proteomics - Immunomonitoring - Biological Resource Centre

13 Clinical trials Inclusions per year (phase I and I-II) 60 BREAST; 48 OTHER SOLID TUMORS; 43 OTHER HEME M,; PROSTATE; NB inclus MDS; 33 ACUTE LEUKEMIA; NHL; immunotherapy cytotoxics mabs targeted inhibitors

14 Networks and coordinated projects - National and international collaborations - UNICANCER - Canceropôle PACA - SIRIC PACA OUEST - MiMAbs, CALYM, CRYOSTEM

15 recherche soins

16 Pharmacology Candidate profiling Structural studies. Animal models Pathological phenotypes Surrogate models Specific transgenic models PHYSIOLOGICAL HYPOTHESIS Expression studies Normal & pathological tissues HT antibody platform VALIDATED TARGET ANTIBODY CANDIDATE (M0) Clinical pharmacology Immune monitoring Biomarkers Functional assays

17 Valorisation - Arylcoumarine derivatives and based oncology drug. Fedorov, A.Y.; Sitnikov, N.S.; Vodovozova, E.L.V, Moiseeva, E.V.; Boldyrev, I.A.; Kuznetsova, N.Y.R.; Beletskaya I.P.; Combes, S. RU (C1), Derivatives of 4-arylcoumarin and 4-arylquinoline as inhibitors of drug transporters and their preparation and use as antineoplastic agents. Combes, S.; Boutonnat, J.; McLeer-Florin, A.; Daras, E.; Peyrot, V.; Fedorov, A. PCT int. Appl. 2012, WO A New apoptosis inducing compounds. Mezil, L.; Berruyer-Pouyet, C.; Cabaud, O.; Josselin, E.; Combes, S.; Brunel, J.-M.; Viens, P.; Colette, Y.; Birnbaum, D.; Lopez, M. Brevet demande n , Use of small molecule inhibitors/activators in combination with (deoxy)nucleoside or (deoxy)nucleotide analogs for treatment of cancer and hematological malignancies or viral infections. S Audebert, P Dubreuil, L Gros. AB Science. Filed in Methods and pharmaceuticals compositions for treating breast cancers. T. Guenneau-Puvirajesinghe, F. Bertucci, JP Borg. Inserm EP / March ASXL1 as a new diagnostic marker of myeloid neoplasms. Olive D, Gelsi-Boyer. Inserm/Ipsogen. WO (A1) Human Anti-ICOS mab as a new therapeutic option for Graft-vs-Host-Disease. September EP New markers of breast tumors from the luminal B subtype. Birnbaum D, Chaffanet M, Ginestier C, Adelaïde J, Sircoulomb F. Inserm, Aix-Marseille University, Institut Paoli Calmettes. WO 2012/ A1 - New apoptosis inducing compounds. PCT/EP2012/ Oct, 4th, Novel antigen peptides and uses thereof. PCT/EP2012/ May, 31st, Oligonucleotide Based Aggregates as Responsive Nanomaterials for Drug Carrier. Oumzyl, K., Acunzo, J., Rocchi, P and Barthelemy, P. European patent submitted via inserm transfert EB13061 (2013). - Amphiphile oligonucleotide conjugates for the treatment of human disease. Oumzyl, K., Acunzo, J., Rocchi, P and Barthelemy, P. European patent submitted via inserm transfert EB13035 (2013). - Methods for selecting binders by phage-display and masked selection. Baty D, Chames P. EP ( ) - Methods for preparing single domain antibody microarrays. Baty D, Chames P, Even- Desrumeaux K. WO/2013/ ( ) - Antigen binding formats for use in therapeutic treaments or diagnostic assays. Baty D, Chartier M, Chames P, Kerfelec B, Rozan C. WO/2012/ ( ) - Procédé et kit de ligation d'adn associant les protéines humaines XRCC4 et XLF avec une ligase d origine microbienne. International Application No. PCT/FR2012/ filed on October 19th, Design of Triplex Forming Tag cassettes and the corresponding Triplex Forming Oligonucleotide probes. S. Fujii, A. Isogawa, R. Fuchs / 01/06/2012/ Brevet européen dépôt Numéro d'enregistrement: Big Pharmas 3 start-ups en 2016