Targeting PLK1 as a novel chemopreventive approach to eradicate preneoplastic mucosal changes in the head and neck

// D. Vicky de Boer 1 , Sanne R. Martens-de Kemp 1 , Marijke Buijze 1 , Marijke Stigter-van Walsum 1 , Elisabeth Bloemena 2, 3 , Ralf Dietrich 4 , C. Rene Leemans 1 , Victor W. van Beusechem 5 , Boudewijn J.M. Braakhuis 1 and Ruud H. Brakenhoff 1 1 Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands 2 Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands 3 Department of Maxillofacial Surgery/Oral Pathology, Academic Center for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands 4 German Fanconi-Anemia-Help e.V., Unna-Siddinghausen, Germany 5 Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands Correspondence to: Ruud H. Brakenhoff, email: rh.brakenhoff@vumc.nl Keywords: preneoplastic fields, head and neck squamous cell carcinoma, siRNA screening, targeted treatment, polo-like kinase 1 Received: November 01, 2016     Accepted: March 30, 2017     Published: May 16, 2017 ABSTRACT Head and neck squamous cell carcinomas (HNSCC) and local relapses thereof develop in preneoplastic fields in the mucosal linings of the upper aerodigestive tract. These fields are characterized by tumor-associated genetic changes, are frequently dysplastic and occasionally macroscopically visible. Currently, no adequate treatment options exist to prevent tumor development. Array-based screening with a panel of tumor-lethal small interfering RNAs (siRNAs) identified Polo-like kinase 1 ( PLK1 ) as essential for survival of preneoplastic cells. Inhibition of PLK1 caused cell death of preneoplastic and HNSCC cells, while primary cells were hardly affected. Both siRNAs and small molecule inhibitors caused a strong G2/M cell cycle arrest accompanied by formation of monopolar spindles. In a xenografted mouse model PLK1 caused a significant tumor growth delay and cures, while chemoradiation had no effect. Thus, PLK1 seems to be a promising target for chemopreventive treatment of preneoplastic cells, and could be applied to prevent HNSCC and local relapses.