• Cancer letters · Mar 2014

    NVP-BEZ235, a dual PI3K/mTOR inhibitor, inhibits osteosarcoma cell proliferation and tumor development in vivo with an improved survival rate.

    • Bérengère Gobin, Séverine Battaglia, Rachel Lanel, Julie Chesneau, Jérôme Amiaud, Françoise Rédini, Benjamin Ory, and Dominique Heymann.
    • INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France.
    • Cancer Lett. 2014 Mar 28;344(2):291-8.

    AbstractDespite recent improvements in chemotherapy and surgery, the problem of non-response osteosarcoma to chemotherapy remains, and is a parameter that is critical for prognosis. The present work investigated the therapeutic value of NVP-BEZ235, a dual class I PI3K/mTOR inhibitor. NVP-BEZ235 inhibited osteosarcoma cell proliferation by inducing G0/G1 cell cycle arrest with no caspase activation. In murine pre-clinical models, NVP-BEZ235 significantly slowed down tumor progression and ectopic tumor bone formation with decreased numbers of Ki67(+) cells and reduced tumor vasculature. Finally, NVP-BEZ235 considerably improved the survival rate of mice with osteosarcoma. Taken together, the results of the present work show that NVP-BEZ235 exhibits therapeutic interest in osteosarcoma and may be a promising adjuvant drug for bone sarcomas.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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