Abstract 1161: COX-2 blockade improves efficacy of VEGF-targeting drugs
| Autor: | Stefanie Sawall, Miguel Cubas-Cordova, Victoria Gensch, Florian Udonta, Mark Wroblewski, Klaus Pantel, Sonja Loges, Isabel Ben Batalla, Carsten Bokemeyer |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Cancer Research. 74:1161-1161 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Efficacy of anti-angiogenic drugs is hampered by hypoxia-induced resistance. Because cyclooxygenase-2 (Cox-2) is upregulated in hypoxic conditions we analyzed mRNA expression levels of cyclooxygenase-1 (Cox-1) and Cox-2 in GFP+ FACS-sorted tumor cells from 4T1 tumors after treatment with anti-VEGFR2 antibodies (DC101) or with sunitinib. Cox-2 but not Cox-1 mRNA was upregulated by 2.3-fold upon anti-angiogenic treatment. In addition we found 5.2-fold increased prostaglandin E2 levels in 4T1 tumors after anti-angiogenic therapy. We hypothesized that concomitant blockade of Cox-2 could increase efficacy of anti-angiogenic agents. Therefore we treated 4T1 tumor-bearing mice with sunitinib or DC101 alone and in combination with acetylsalicyclic acid (ASA). We found that single treatment with ASA or angiogenesis inhibitors inhibited tumor growth and that combined inhibition of Cox-2 and VEGF(R) signaling exerted additive therapeutic efficacy (n=5; 1142±84 (ASS); 1148±78 (Sunitnib) vs. 63±5 mg (combination); p In addition, Cox-2 and PGE2 can promote tumor angiogenesis. This alternative pro-angiogenic pathway would be enhanced by increased Cox-2 expression and PGE2 levels and could contribute to resistance against anti-angiogenic treatments. In line with this hypothesis the MVD was decreased 4T1 tumors treated with combined Cox-2 and VEGF blockade compared to the respective monotherapy (n=7; 31±2.4 (Sunitinib); 28.58±0.83 (ASS) vs. 9.67±1.71 (combination); p Citation Format: Isabel Ben Batalla, Miguel Cubas-Cordova, Florian Udonta, Mark Wroblewski, Stefanie Sawall, Victoria Gensch, Klaus Pantel, Carsten Bokemeyer, Sonja Loges. COX-2 blockade improves efficacy of VEGF-targeting drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1161. doi:10.1158/1538-7445.AM2014-1161 |
| Databáze: | OpenAIRE |
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