Gene Expression Analysis Reveals Distinct Pathways of Resistance to Bevacizumab in Xenograft Models of Human ER-Positive Breast Cancer

Autor: Chirayu P. Goswami, Mircea Ivan, George W. Sledge, Rachel A. Toroni, Bogdan Tanasa, Usha Sirimalle, Kerry L. Sanders, Yesim Gökmen-Polar, Changyu Shen, Sunil Badve, Rutika Mehta, Lang Li
Rok vydání: 2014
Předmět:
Zdroj: Journal of Cancer
ISSN: 1837-9664
Popis: Bevacizumab, the recombinant antibody targeting vascular endothelial growth factor (VEGF), improves progression-free but not overall survival in metastatic breast cancer. To seek further insights in resistance mechanisms to bevacizumab at the molecular level, we developed VEGF and non-VEGF-driven ER-positive MCF7-derived xenograft models allowing comparison of tumor response at different timepoints. VEGF gene (MV165) overexpressing xenografts were initially sensitive to bevacizumab, but eventually acquired resistance. In contrast, parental MCF7 cells derived tumors were de novo insensitive to bevacizumab. Microarray analysis with qRT-PCR validation revealed that Follistatin (FST) and NOTCH were the top signaling pathways associated with resistance in VEGF-driven tumors (P
Databáze: OpenAIRE