Ekaagra Kesarwani

1 1Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales 2145, Australia; 2Department of Chemistry, University of Colorado, Boulder, Colorado 80309, USA; 3Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA Corresponding author: hpickett{at}cmri.org.au ↵4 These authors contributed equally to this work. Footnotes Supplemental material is available for this article.

Abstract The Eyes Absent family of protein phosphatases (EYA1-4) are aberrantly expressed and tumour-promoting across many devastating cancers of neurological origin affecting both children and adults. It has recently been demonstrated that EYA1 and EYA4 promote tumour cell survival by increasing the active pool of Polo-like kinase 1 (PLK1) molecules. This discovery provides a rationale for the therapeutic combination of EYA inhibitors with direct, ATP-competitive, PLK1 inhibitors.