Cell Cycle Inhibitors for the Treatment of Acute Myeloid Leukemia: A Review of Phase 2 & 3 Clinical Trials

Introduction: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with poor long term outcomes. Cytotoxic chemotherapy remains the backbone of therapy especially among younger patients; however the effective incorporation of targeted therapies continues to be an area of active research in an effort to improve response durations and survival. Cell cycle inhibitors (CCI) are a novel class of agents which may be of particular interest for development in patients with AML. Areas covered: We will review the concept of CCIs and available pre-clinical and clinical data in the treatment of AML both in North America and abroad. Specific drug targets reviewed include cyclin D kinase, Aurora kinase, CHK1, and WEE1. Expert opinion: Utilization of CCIs in AML is an emerging approach that has shown promise in pre-clinical models. It has been challenging to translate this concept into clinical success due to marginal single-agent activity and toxicity profiles, however clinical evaluation remains ongoing. Addition of these agents to cytotoxic chemotherapy and other targeted therapies provides a potential combinatorial path forward for this novel class of therapies. Developing optimal combinations while balancing toxicity are among the top clinical challenges to overcome before we can anticipate adoption of these agents into the armamentarium of AML therapy.