Differentiation Therapy

Overview Abnormal differentiation is one of the main features of human cancers, especially in hematological malignancies. Many aberrant genetic and epigenetic factors have been shown to disrupt the regulation of cell differentiation in a variety of cancers and play an important role in oncogenesis. Differentiation therapy refers to the application of therapeutic agents selectively targeting the key molecules involved in the process of cell differentiation, leading to the restoration of normal cellular homeostasis and the eventual clearance of cancer cells. Over the past four decades, investigations of the molecular mechanisms underlying cancer cell differentiation arrest or blockage have allowed the identification of an array of drug targets. On the other hand, many physiological or pharmacological agents have been tested using in vitro and in vivo systems as the inducers of differentiation and maturation of cancer cells. The translational research in this field has gradually turned the differentiation therapy from a concept to clinical practices. The most successful model of cancer differentiation therapy is the development of synergistic targeted therapy for acute promyelocytic leukemia (APL) with all‐trans‐retinoic acid (ATRA) and arsenic trioxide (ATO). This article discusses the basic theories of differentiation therapy and the clinical achievements of this therapeutic approach.