@entity7416 Inhibition Combined with XXXX Improved Antitumor and Antiangiogenic Response in Preclinical Models of @entity43 .

@entity43 @entity7 @entity5 @entity2857 @entity319 @entity50951 @entity687 @entity7416
UNASSIGNED: Antiangiogenic therapy is important for the treatment of gynecological @entity5 . However, the therapeutic benefit derived from these treatments is transient, predominantly due to the selective activation of compensatory proangiogenic pathways that lead to rapid development of resistance. We aimed to identify and target potential alternative signaling to @entity7 ( @entity7 ) therapy, with a view toward developing a combination of antiangiogenic agents to provide extended therapeutic benefits. We developed a preclinical in vivo phenotypic resistance model of @entity43 resistant to antiangiogenic therapy. We measured dynamic changes in secreted chemokines and angiogenic signaling in @entity5 and plasma in response to anti- @entity7 treatment, as @entity5 advanced from the initial responsive phase to progressive disease. In @entity5 that progressed following @entity2857 treatment, gene and protein expression levels of proangiogenic CXC chemokines and their receptors were significantly elevated, compared with responsive @entity5 . The @entity687 ( @entity687 ), also known as @entity687 ( @entity687 ) increase was time-dependent and coincided with the dynamics of @entity5 progression. We used @entity50951 , a pharmacological inhibitor of @entity7416 ( @entity7416 ), to disrupt the CXC chemokine-mediated functions of @entity43 cells in in vitro assays of cell growth inhibition, spheroid formation, and cell migration. The combination of @entity7416 inhibitor with @entity2857 led to a synergistic inhibition of cell growth in vitro, and further stabilized @entity5 progression following @entity2857 in vivo. Our results suggest that @entity7416 -mediated chemokines may represent an important compensatory pathway that promotes resistance to antiangiogenic therapy in @entity43 . Thus, simultaneous blockage of this proangiogenic cytokine pathway using @entity7416 inhibitors and the @entity319 ( @entity319 ) pathway could improve the outcomes of antiangiogenic therapy.
