Institut de recherche biomédicale
     
    Vous êtes ici : Accueil / L'Institut / Séminaires / A key step forward in the prevention of chemoresistance in osteosarcoma

    A key step forward in the prevention of chemoresistance in osteosarcoma

    Webinaire de l'Institut Cochin

    Jeudi 3 juin 2021 - 12h00 - Pour obtenir le lien d'accès Zoom, envoyez un mail à

     


    Olivia Fromigue

    Inserm UMR981, Gustave Roussy, Villejuif, France

     

     invitée par Benoit Miotto


    Résumé

    Osteosarcoma is the most common form of primary bone malignancy, excluding bone marrow tumors. Diagnosed in children and young adults, it is a disease as rare as severe. A huge rate of complex chromosomic aberrations prevents the development of targeted therapy. The cure rate did not improve in the last 4 decades, with dismal prognosis for metastatic, chemoresistant and relapsed disease. Our strategy was to focus on a physiological reaction engaged by any cells exposed to toxic exogenous compounds: the detoxication. Clinical samples derived from chemonaive biopsies revealed that tumor cells expressing low MT2A (metallothionein 2A) levels correspond to good prognostic (good responder patients with longer survival rate), whereas high MT2A levels were associated with adverse prognosis (poor responder patients). We deeper investigated the molecular mechanisms of this protective action and highlighted an effect partially mediated by modulation of bioavailable zinc levels. Taken together, our data suggest that MT2A may be a predictive biomarker of resistance to chemotherapy, and provide with preclinical rational for MT2A targeting as a therapeutic strategy for enhancing anti-tumor treatment of innate chemo-resistant osteosarcoma cells.

     

    Quelques publications

    • Stefanovska B, Vicier CE, Dayris T, Ogryzko V, Scott V, Bouakka I, Delaloge S, Rocca A, Le Saux O, Trédan O, Bachelot T, André F, Fromigué O. Rapalog-Mediated Repression of Tribbles Pseudokinase 3 Regulates Pre-mRNA Splicing. Cancer Res. 2020 Jun 1;80(11):2190-2203.
    • Mangelinck A, da Costa MEM, Stefanovska B, Bawa O, Polrot M, Gaspar N, Fromigué O. MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma. Sci Rep. 2019 Aug 23;9(1):12301.
    • Marques da Costa ME, Marchais A, Gomez-Brouchet A, Job B, Assoun N, Daudigeos-Dubus E, Fromigué O, Santos C, Geoerger B, Gaspar N. In-Vitro and In-Vivo Establishment and Characterization of Bioluminescent Orthotopic Chemotherapy-Resistant Human Osteosarcoma Models in NSG Mice. Cancers (Basel). 2019 Jul 17;11(7):997.
    • Habel N, Stefanovska B, Carène D, Patiño-Garcia A, Lecanda F, Fromigué O. CYR61 triggers osteosarcoma metastatic spreading via an IGF1Rβ-dependent EMT-like process. BMC Cancer. 2019 Jan 14;19(1):62. doi: 10.1186/s12885-019-5282-4.