Abstract 1371: Systems biology analysis to identify biomarkers for lenvatinib in the preclinical cancer cell line panels

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.1371-1371
• Main Authors: Dezso, Zoltan, Ino, Mitsuhiro, Minoshima, Yukinori, Tohyama, Osamu, Sugi, Naoko Hata, Agoulnik, Sergei, Oda, Yoshiya, Funahashi, Yasuhiro
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-1371

Objectives: Lenvatinib mesilate (lenvatinib) is the selective inhibitor of VEGFR1-3, and other proangiogenic and oncogenic pathway-related RTKs including fibroblast growth factor receptors (FGFR1-4), the platelet-derived growth factor receptor (PDGFR) α, KIT, and RET. Lenvatinib have been tested in several clinical trials, such as thyroid cancer and hepatocellular carcinoma in Ph3, but biomarkers to predict lenvatinib activity were not established. We performed a preclinical systems biology approach to identify biomarkers predictive of lenvatinib sensitivity in endometrial cell lines. Methods: We performed gene expression profiling using Affimetrix Human exon 1.0 ST array and targeted exon sequencing of 1,163 genes using Illumina sequencer in 19 endometrial cell lines. In vitro anti-proliferation activity (IC50) and in vivo anti-tumor activity of lenvatinib were determined in the panel. Besides, we did siRNA kinase library screening to classify the cell lines into two groups by unsupervised hierarchical clustering. We identified genes significantly over-expressed (p value