Emerging cell cycle inhibitors for acute myeloid leukemia

INTRODUCTION: AML therapy remains very challenging despite our increased understanding of its molecular heterogeneity. Outcomes with chemotherapy and targeted therapy remain poor. Targeting cell cycle regulators might complement chemotherapy and targeted therapy and help in improving outcomes. Areas covered: Here we cover the pre-clinical and clinical data for both for cyclin dependent kinase (CDK) and cell-cycle checkpoint inhibitors. While CDK inhibition can inhibit proliferation, checkpoint inhibitors can facilitate cell cycle progression in presence of DNA damage and can induce mitotic catastrophe. Expert opinion: Though the preclinical data for cell cycle inhibitors in AML is compelling, the clinical translation so far has proven to be challenging. This is a reflection of the complexity of both, AML and cell cycle regulators. However, early introduction of cell-cycle active agents in combination with chemotherapy or targeted agents, identifying right sequence of use and identifying right biomarkers might pave the way into successful clinical translation.