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Non-genomic events determining the sensitivity of hemopoietic malignancies to glucocorticoid-induced apoptosis

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Glucocorticoid (GC) hormones have been introduced as therapeutic agents in blood cancers six decades ago. The effectiveness of GC treatment stems from its ability to induce apoptotic death of hemopoietic cells. A major impediment in GC therapy is the acquisition of resistance to the drug upon repeated treatment. In addition, some blood cancers are a priori resistant to GC therapy. Usually, resistance to GC correlates with poor prognosis. Albeit the wide use of GC in clinical practice, their mode of action is not fully understood. The cellular response to GC is initiated by its binding to the cytosolic GC receptor (GR) that translocates to the nucleus and modulates gene expression. However, nuclear activities of GR occur in both apoptosis-sensitive and apoptosis-resistant cells. These apparent controversies can be resolved by deciphering non-genomic effects of GCs and the mode by which they modulate the apoptotic response. We suggest that non-genomic consequences of GC stimulation determine the cell fate toward survival or death. Understanding the cellular mechanisms of GC apoptotic sensitivity contributes to the development of new modalities for overcoming GC resistance.

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Acknowledgments

The authors wish to thank Dr. Ronit Vogt-Sionov, Hali Spokoini, and Prof. Ingrid Herr for their contribution. The study described in this review was supported in part by the German-Israel Foundation (GIF) and Concern Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. The Lautenberg Center for Immunology and Cancer Research, IMRIC, The Hebrew University-Hadassah Medical School, POB: 12272, 91120, Jerusalem, Israel

    Shlomit Kfir-Erenfeld & Eitan Yefenof

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  1. Shlomit Kfir-Erenfeld
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  2. Eitan Yefenof
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Correspondence to Shlomit Kfir-Erenfeld.

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This paper is a Focussed Research Review based on a presentation given at the Third International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2013), held in Krakow, Poland, 22nd–25th April 2013. It is part of a CII series of Focussed Research Reviews and meeting report.

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Kfir-Erenfeld, S., Yefenof, E. Non-genomic events determining the sensitivity of hemopoietic malignancies to glucocorticoid-induced apoptosis. Cancer Immunol Immunother 63, 37–43 (2014). https://doi.org/10.1007/s00262-013-1477-8

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  • DOI: https://doi.org/10.1007/s00262-013-1477-8

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