Volasertib in Cancer Therapy: From Mechanism to Clinical Potential

Volasertib is a second-generation, selective inhibitor of polo-like kinase 1 (PLK1), created for targeted therapy in cancer treatment, particularly acute myeloid leukemia (AML). PLK1 plays a crucial role in regulating mitosis and is often overexpressed in cancerous cells, which makes it a promising target for therapy. By inhibiting PLK1-mediated progression through mitosis, volasertib prompts G2/M cell-cycle arrest and leads to apoptosis. Preclinical studies showed significant antitumor effects, prompting further clinical investigations in both hematological and solid tumors. In AML, volasertib exhibited clinical effectiveness, particularly when paired with low-dose cytarabine in elderly or unfit patients; however, hematologic toxicity hindered its continued development. Despite some encouraging results in early-phase trials, phase III studies did not show a survival advantage, underlining the difficulties associated with using PLK1 inhibition as a standalone treatment. This review outlines the mechanism of action, clinical findings, limitations, and future outlook for volasertib, stressing the insights gained for developing next-generation PLK1 inhibitors in cancer therapy.