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.

分化疗法的概念源于激素或细胞因子可能促进离体分化的事实。从而不可逆地改变癌细胞的表型。它的标志性成功是治疗急性早幼粒细胞白血病（APL），该病现在可通过视黄酸（RA）和砷的联合治疗而高度治愈。最近，已经鉴定出可以在多种原发性肿瘤细胞中分化的药物，这表明它们在临床上是有用的。本文通过评估终末成熟和自我更新丧失的各自作用，分析了RA或砷在APL中临床成功的基础。通过回顾药物诱导肿瘤细胞分化的其他成功实例，提出了将分化药物转化为更有效疗法的新方法。