Vosaroxin: a new valuable tool with the potential to replace anthracyclines in the treatment of AML?

Introduction: Despite significant advances in diagnosis and supportive care, the majority of patients diagnosed with acute myeloid leukemia (AML) ultimately die of their disease. Standard intensive induction treatment continues to comprise cytarabine and a topoisomerase II (topo II) poison, usually an anthracycline. Vosaroxin , a novel first-in-class quinolone derivative has been developed for use in the treatment of AML as a new-generation topo II inhibitor. It has shown promising activity as a monotherapy and also in combination with intermediate dose cytarabine (IDAC) in relapsed and refractory patient cohorts with minimal toxicity and good tolerability. Areas covered: The authors discuss the mechanism of action of vosaroxin, the pharmacokinetics, safety and tolerability, preclinical and clinical trial results available as well as areas of ongoing research. Expert opinion: Vosaroxin has shown efficacy as a novel cytotoxic agent, and despite a similar mechanism of action has significant advantages over anthracyclines. It evades common resistance pathways of p53 and P-glycoprotein (P- gp) and does not appear to generate significant reactive oxygen species (ROS) associated with these agents. Should future investigation confirm its efficacy and advantageous safety profile, vosaroxin could potentially replace older generation topoisomerase poisons in the treatment of AML and other malignant conditions

Cell cycle kinases as therapeutic targets for cancer.

Several families of protein kinases orchestrate the complex events that drive the cell cycle, and their activity is frequently deregulated in hyperproliferative cancer cells. Although several molecules that inhibit cell cycle kinases have been developed and clinically screened as potential anticancer agents, none of these has been approved for commercial use and an effective strategy to specifically control malignant cell proliferation has yet to be established. However, recent genetic and biochemical studies have provided information about the requirement for certain cell cycle kinases by specific tumours and specialized tissue types. Here, we discuss the potential and limitations of established cell cycle kinases as targets in anticancer drug discovery as well as novel strategies for the design of new agents