Update on rational targeted therapy in AML

Abstract

Acute myeloid leukemia (AML) remains a challenge to both patients and clinicians. Despite improvements in our understanding of the disease, treatment has changed minimally and outcomes remain poor for the majority of patients. Within the last decade, there have been an increasing number of potential targets and pathways identified for development in AML. The classes of agents described in this review include but are not limited to epigenetic modifiers such as IDH inhibitors, BET inhibitors, and HDAC inhibitors as well as cell cycle and signaling inhibitors such as Aurora kinase inhibitors and CDK inhibitors. While the developments are encouraging, it is unlikely that targeting a single pathway will result in long-term disease control. Accordingly, we will also highlight potential rational partners for the novel agents described herein.

Keywords: Aurora kinase; BET; BH3-mimetic; DOT1L; Flavopiridol; HDAC inhibitors; Hedgehog; High-risk AML; IDH; Idasanutlin; LSD1; Palbociclib; Pevonedistat; Rigosertib; Tosedostat; Venetoclax; Volasertib; Wee1.