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

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. C...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget Vol. 8; no. 58; p. 97928
Main Authors: de Boer, D Vicky, Martens-de Kemp, Sanne R, Buijze, Marijke, Stigter-van Walsum, Marijke, Bloemena, Elisabeth, Dietrich, Ralf, Leemans, C René, van Beusechem, Victor W, Braakhuis, Boudewijn J M, Brakenhoff, Ruud H
Format: Journal Article
Language:English
Published: United States 17.11.2017
Subjects:
polo-like kinase 1
siRNA screening
preneoplastic fields
head and neck squamous cell carcinoma
targeted treatment
ISSN:1949-2553, 1949-2553
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 ( ) 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.17880