{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jaiprasart P"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["99-114"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6967771"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["VEGF-mediated tumor angiogenesis is a validated clinical target in many cancers, but modest efficacy and rapid development of resistance are major challenges of VEGF-targeted therapies. To establish a molecular signature of this resistance in ovarian cancer, we developed preclinical tumor models of adaptive resistance to chronic anti-VEGF treatment. We performed RNA-seq analysis and reverse-phase protein array to compare changes in gene and protein expressions in stroma and cancer cells from resistant and responsive tumors. We identified a unique set of stromal-specific genes that were strongly correlated with resistance phenotypes against two different anti-VEGF treatments, and selected the apelin/APJ signaling pathway for further <i>in vitro</i> validation. Using various functional assays, we showed that activation of apelin/APJ signaling reduces the efficacy of a VEGF inhibitor in endothelial cells. In patients with ovarian cancer treated with bevacizumab, increased expression of apelin was associated with significantly decreased disease-free survival. These findings link signature gene expressions with anti-VEGF response, and may thus provide novel targetable mechanisms of clinical resistance to anti-VEGF therapies."],"journal":["Oncotarget"],"pubmed_title":["Identification of signature genes associated with therapeutic resistance to anti-VEGF therapy."],"pmcid":["PMC6967771"],"funding_grant_id":["P30 CA016672","R50 CA221675","P20 GM103639"],"pubmed_authors":["Jaiprasart P","Woo S","Devapatla B","Neelakantan D","Dogra S"],"additional_accession":[]},"is_claimable":false,"name":"Identification of signature genes associated with therapeutic resistance to anti-VEGF therapy.","description":"VEGF-mediated tumor angiogenesis is a validated clinical target in many cancers, but modest efficacy and rapid development of resistance are major challenges of VEGF-targeted therapies. To establish a molecular signature of this resistance in ovarian cancer, we developed preclinical tumor models of adaptive resistance to chronic anti-VEGF treatment. We performed RNA-seq analysis and reverse-phase protein array to compare changes in gene and protein expressions in stroma and cancer cells from resistant and responsive tumors. We identified a unique set of stromal-specific genes that were strongly correlated with resistance phenotypes against two different anti-VEGF treatments, and selected the apelin/APJ signaling pathway for further <i>in vitro</i> validation. Using various functional assays, we showed that activation of apelin/APJ signaling reduces the efficacy of a VEGF inhibitor in endothelial cells. In patients with ovarian cancer treated with bevacizumab, increased expression of apelin was associated with significantly decreased disease-free survival. These findings link signature gene expressions with anti-VEGF response, and may thus provide novel targetable mechanisms of clinical resistance to anti-VEGF therapies.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2026-05-07T18:18:26.612Z","creation":"2020-05-22T08:51:58Z"},"accession":"S-EPMC6967771","cross_references":{"pubmed":["32002127"],"doi":["10.18632/oncotarget.27307"]}}