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Gene expression changes during resistance toward vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma (RCC)


ABSTRACT: This study was performed to understand the gene expression changes that accompany treatment of renal cell carcinoma (RCC) with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Human RCC cell lines were implanted into the flanks of nude beige mice, allowed to reach 12mm in long axis, and then treated with TKIs (sunitinib or sorafenib). Tumors were excised at 2 timepoints (prior to any therapy and at the 20mm endpoint of the study) and gene expression analysis was performed. Sunitinb or sorafenib were administered to mice bearing either 786-O or A498 xenografts. Mice were sacrificed and tumors excised for RNA extraction at pretreatment size of 12mm, or at 20mm, the mandated maximum tumor size allowed at our institution.

ORGANISM(S): Homo sapiens

SUBMITTER: Manoj Bhasin 

PROVIDER: E-GEOD-64052 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer.

Zhang Liang L   Wang Xiaoen X   Bullock Andrea J AJ   Callea Marcella M   Shah Harleen H   Song Jiaxi J   Moreno Kelli K   Visentin Barbara B   Deutschman Douglas D   Alsop David C DC   Atkins Michael B MB   Mier James W JW   Signoretti Sabina S   Bhasin Manoj M   Sabbadini Roger A RA   Bhatt Rupal S RS  

Clinical cancer research : an official journal of the American Association for Cancer Research 20150114 8


<h4>Purpose</h4>VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic renal cell carcinoma (RCC). However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for patients with TKI-naïve or -resistant RCC.<h4>Experimental design</h4>In this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in a murine model and discovered that the SPHK-S1P pathway is upregulated at the time of  ...[more]

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