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Perspectives on inhibiting mTOR as a future treatment strategy for hematological malignancies

Leukemia volume 24, pages 1686–1699 (2010)Cite this article

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Abstract

Mammalian target of rapamycin (mTOR) is a protein kinase implicated in the regulation of various cellular processes, including those required for tumor development, such as the initiation of mRNA translation, cell-cycle progression and cellular proliferation. In a wide range of hematological malignancies, the mTORC1 signaling pathway has been found to be deregulated and has been designed as a major target for tumor therapy. Given that pre-clinical studies have clearly established the therapeutic value of mTORC1 inhibition, numerous clinical trials of rapamycin and its derivates (rapalogs) are ongoing for treatment of these diseases. At this time, although disease stabilization and tumor regression have been observed, objective responses in some tumor types have been modest. Nevertheless, some of the mechanisms underlying cancer-cell resistance to rapamycin have now been described, thereby leading to the development of new strategy to efficiently target mTOR signaling in these diseases. In this review, we discuss the rationale for using mTOR inhibitors as novel therapies for a variety of hematological, malignancies with a focus on promising new perspectives for these approaches.

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Acknowledgements

This work was supported by grants from the Ligue Nationale Contre le Cancer (LNCC, laboratoire associé), the Institut National du Cancer (INCa), the Association Laurette Fugain. LW is recipient of grants from Institut National de la Santé Et de la Recherche Médicale (INSERM).

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Authors and Affiliations

  1. Département d'Immunologie-Hématologie, Institut Cochin, Université Paris Descartes, CNRS, UMR8104, Paris, France

    N Chapuis, J Tamburini, A S Green, L Willems, V Bardet, S Park, C Lacombe, P Mayeux & D Bouscary

  2. INSERM, U1016, Paris, France

    N Chapuis, J Tamburini, A S Green, L Willems, V Bardet, S Park, C Lacombe, P Mayeux & D Bouscary

  3. Service d'Hématologie Biologique, Hôpital Cochin, AP-HP, Paris, France

    N Chapuis, V Bardet & C Lacombe

  4. Service de Médecine Interne-UF d'Hématologie, Hôpital Cochin, Paris, France

    J Tamburini, L Willems, S Park & D Bouscary

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  1. N Chapuis
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  2. J Tamburini
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  3. A S Green
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  4. L Willems
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  7. C Lacombe
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  9. D Bouscary
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Correspondence to D Bouscary.

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Chapuis, N., Tamburini, J., Green, A. et al. Perspectives on inhibiting mTOR as a future treatment strategy for hematological malignancies. Leukemia 24, 1686–1699 (2010). https://doi.org/10.1038/leu.2010.170

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  • DOI: https://doi.org/10.1038/leu.2010.170

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