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Differentiation therapy revisited

Abstract

The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukaemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Recently, drugs that trigger differentiation in a variety of primary tumour cells have been identified, suggesting that they are clinically useful. This Opinion article analyses the basis for the clinical successes of RA or arsenic in APL by assessing the respective roles of terminal maturation and loss of self-renewal. By reviewing other successful examples of drug-induced tumour cell differentiation, novel approaches to transform differentiating drugs into more efficient therapies are proposed.

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Figure 1: Timeline of differentiation therapy.
Figure 2: Acute promyelocytic leukaemia pathogenesis and response to targeted therapies.
Figure 3: Schematic representation of the targets discussed in this Opinion article.

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Acknowledgements

The author's laboratory is supported by Collège de France, INSERM, Centre National de la Recherche Scientifique (CNRS), Université Paris-Diderot, Ligue Contre le Cancer, Institut National du Cancer and the European Research Council. The author apologizes to investigators whose work could not be cited because of space constraints. The author thanks F. Maloumian for help with the figures and friends and colleagues for critical reading of the manuscript, in particular A. Bazarbachi, O. Hermine, L. Degos, P. Fenaux and V. Lallemand-Breitenbach.

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Correspondence to Hugues de Thé.

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de Thé, H. Differentiation therapy revisited. Nat Rev Cancer 18, 117–127 (2018). https://doi.org/10.1038/nrc.2017.103

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