Differentiation therapy revisited

de The, H

de The, H (reprint author), PSL Res Univ, Coll France, F-75005 Paris, France.; de The, H (reprint author), Univ Paris Diderot, Sorbonne Paris Cite, INSERM UMR 944, Equipe Labellisee Ligue Natl Canc, F-75010 Paris, France.; de The, H (reprint author), Univ

NATURE REVIEWS CANCER, 2018; 18 (2): 117


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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