Update on aurora kinase targeted therapeutics in oncology

Abstract

Introduction: Mammalian cells contain three distinct serine/threonine protein kinases with highly conserved catalytic domains, including aurora A and B kinases that are essential regulators of mitotic entry and progression. Overexpression of aurora A and/or B kinase is associated with high proliferation rates and poor prognosis, making them ideal targets for anticancer therapy. Disruption of mitotic machinery is a proven anticancer strategy used by multiple chemotherapeutic agents. Numerous small molecule inhibitors of the aurora kinases have been discovered and tested in vivo and in vitro, with a few currently in Phase II testing.Areas covered: This review provides the reader with updated results from both preclinical and human studies for each of the aurora kinase inhibitors (AKIs) that are currently being investigated. The paper also covers in detail the late breaking and Phase I data presented for AKIs thereby allowing the reader to compare and contrast individual and class-related effects of AKIs.Expert opinion: While the successful development and approval of an AKI for anticancer therapy remains unresolved, preclinical identification of resistant mechanisms would help in designing better early phase clinical trials where relevant combinations may be evaluated prior to Phase II testing. The authors believe that aurora kinases are important anticancer targets that operate in collaboration with other oncogenes intimately involved in uncontrolled tumor proliferation and by providing a unique, targeted and complimentary anticancer mechanism, expand the available armamentarium against cancer.