@Article{096504021X16130322409507,
AUTHOR = {Huan Ma, Cong Nie, Ying Chen, Jinmiao Li, Yanjie Xie, Zhixin Tang, Yang Gao, Siming Ai, 
Yuxiang Mao, Qian Sun, Rong Lu},
TITLE = {Therapeutic Targeting PLK1 by ON-01910.Na Is Effective  in Local Treatment of Retinoblastoma},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {7-8},
PAGES = {745--761},
URL = {http://www.techscience.com/or/v28n7-8/48465},
ISSN = {1555-3906},
ABSTRACT = {Cell cycle deregulation is involved in the pathogenesis of many cancers and is often associated with protein 
kinase aberrations, including the polo-like kinase 1 (PLK1). We used retinoblastoma, an intraocular malignancy that lacks targeted therapy, as a disease model and set out to reveal targetability of PLK1 with a small 
molecular inhibitor ON-01910.Na. First, transcriptomic analysis on patient retinoblastoma tissues suggested 
that cell cycle progression was deregulated and confirmed that PLK1 pathway was upregulated. Next, antitumor activity of ON-01910.Na was investigated in both cellular and animal levels. Cytotoxicity induced by 
ON-01910.Na was tumor specific and dose dependent in retinoblastoma cells, while nontumor cells were 
minimally affected. In three-dimensional culture, ON-01910.Na demonstrated efficient drug penetrability with 
multilayer cell death. Posttreatment transcriptomic findings revealed that cell cycle arrest and MAPK cascade 
activation were induced following PLK1 inhibition and eventually resulted in apoptotic cell death. In Balb/c 
nude mice, a safe threshold of 0.8 nmol intravitreal dosage of ON-01910.Na was established for intraocular 
safety, which was demonstrated by structural integrity and functional preservation. Furthermore, intraocular 
and subcutaneous xenograft were significantly reduced with ON-01910.Na treatments. For the first time, we 
demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. Our 
study is supportive that local treatment of ON-01910.Na may be a novel, effective modality benefiting patients 
with PLK1-aberrant tumors.},
DOI = {10.3727/096504021X16130322409507}
}