The preclinical discovery of vosaroxin for the treatment of acute myeloid leukemia

ABSTRACT

Introduction: Acute myeloid leukemia (AML) represents a disease with a very poor outcome and remains an area of significant unmet need necessitating novel therapeutic strategies. Among novel therapeutic agents, vosaroxin is a first-in-class anticancer quinolone derivative that targets topoisomerase II and induces site-selective double-strand breaks in DNA, leading to tumor cell apoptosis.

Areas covered: Herein, the authors provide a comprehensive review of the preclinical development of vosaroxin. This includes coverage of vosaroxin’s mechanism of action in addition to its pharmacology and of the main studies reported over the past few years with vosaroxin when used to treat adult AML.

Expert opinion: Given that vosaroxin is associated with fewer potential side effects, it may be of benefit to elderly patients with relapsed/refractory AML and to those with additional comorbidities who have previously received an anthracycline and cytarabine combination. Furthermore, vosaroxin also was seen to be active in multidrug-resistant preclinical models. However, further studies have to be performed to better evaluate its place in the armamentarium against AML.

KEYWORDS:

• Vosaroxin
• acute myeloid leukemia
• quinolone
• intercalating agents
• targeted therapy
• prognosis
• relapse

Article highlights

• Vosaroxin is a first-in-class anticancer quinolone derivative that poisons topoisomerase II causing p53 mutation status-independent cell apoptosis.

• Mechanism of action is intercalation into DNA during the G2/M cell division stage, inducing double-strands breaks in GC-rich regions.

• Combination of vosaroxin with cytarabine leads to synergistic effects and activity.

• Phases 1 and 2 studies demonstrated efficacy and tolerability of the drug in AML patients.

• The recent phase 3 VALOR study showed a better CR rate and a better OS when adding vosaroxin to cytarabine in R/R patients ≥60 years of age.

This box summarizes key points contained in the article

Declaration of interest

X Thomas has been a member of the advisory board of Sunesis. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This manuscript has not been funded.