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Research Articles: Therapeutics, Targets, and Development

Comparing Aurora A and Aurora B as molecular targets for growth inhibition of pancreatic cancer cells

¹ College of Pharmacy and ² Arizona Cancer Center, University of Arizona, Tucson, Arizona; ³ Translational Genomics Research Institute, Phoenix, Arizona; and ⁴ Isis Pharmaceuticals, Carlsbad, California

Requests for reprints: Haiyong Han, Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ 85004. Phone: 602-343-8739; Fax: 602-343-8740. E-mail: hhan{at}tgen.org

Abstract

To address the increased need to understand the similarities and differences in targeting Aurora A or Aurora B for the treatment of cancer, we systematically evaluated the relative importance of Aurora A and/or Aurora B as molecular targets using antisense oligonucleotides. It was found that perturbations in Aurora A and Aurora B signaling result in growth arrest and apoptosis preferentially in cancer cells. The biological fingerprints of Aurora A and Aurora B inhibition were compared and contrasted in efforts to identify the superior therapeutic target. Due to the different biological responses, we conclude that each Aurora kinase should be treated as autonomous drug targets, which can be targeted independently or in combination. We observed no advantages to targeting both kinases simultaneously and feel that an Aurora A–targeted therapy may have some beneficial consequences over an Aurora B–targeted therapy, such as mitotic arrest and the rapid induction of apoptosis. [Mol Cancer Ther 2006;5(10):2450–8]

Grant support: American Chemical Society Division of Medicinal Chemistry and Wyeth predoctoral fellowship (S.L. Warner) and NIH grant CA 95031 (D.D. Von Hoff).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4/11/06; revised 7/28/06; accepted 8/16/06.

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