Owing to their integral involvement in cell cycle regulation, the Polo-like
kinase (Plk) family, particularly Plk1, has emerged as an attractive therapeutic target in oncology. In recent years, several Plk1 inhibitors have been developed, with some agents showing encouraging results in early-phase clinical trials. This review focuses on
volasertib (
BI 6727; an investigational agent), a potent and selective Plk inhibitor.
Volasertib has shown promising activity in various
cancer cell lines and xenograft models of human
cancer. Trials performed to date suggest that
volasertib has clinical efficacy in a range of
malignancies, with the most promising results seen in patients with
acute myeloid leukemia (AML). Encouragingly, recent phase II data have demonstrated that
volasertib combined with low-dose
cytarabine (LDAC) was associated with higher response rates and improved event-free survival than LDAC alone in patients with previously untreated AML. Based on these observations, and its presumably manageable safety profile,
volasertib is currently in phase III development as a potential treatment for patients with AML who are ineligible for intensive
remission induction therapy. Given that many patients with AML are of an older age and frail, this constitutes an area of major unmet need. In this review, we discuss the biologic rationale for Plk1 inhibitors in
cancer, the clinical development of
volasertib to date in solid
tumors and AML, and the future identification of
biomarkers that might predict response to
volasertib and help determine the role of this agent in the clinic.