Emerging cell cycle inhibitors for acute myeloid leukemia

ABSTRACT

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.

KEYWORDS:

• Acute myeloid leukemia
• aurora kinase inhibitor
• CHK1
• cyclin dependent kinase
• mitotic catastrophe
• WEE1

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.