Abstract LB-299: Effect of antiangiogenic therapy on tumor growth, vasculature and kinase activity in luminal and basal-like breast cancer xenografts

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8_Supplement; p. LB-299
• Main Authors: Lindholm, Evita, Kristian, Alexandr, Nalvoga, Hawa, Kruger, Kristi, Mælandsmo, Gunhild M., Akslen, Lars A., Engebraaten, Olav
• Format: Journal Article
• Language: English
• Published: 15.04.2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-LB-299

Abstract Angiogenesis is important for the growth and dissemination of solid tumors, and VEGF-A is one of the main stimulators of this process. Bevacizumab binds VEGF and increases the progression-free, but not overall, survival in breast cancer patients treated with chemotherapy. For determining factors of importance for treatment response and resistance, two different human breast cancer xenografts (luminal -and basal-like) were used, which respond differently to antiangiogenic mono -or combination therapy. Both doxorubicin and bevacizumab inhibited tumor growth significantly in basal-like xenografts, but with a superior effect when given in combination. In contrast, luminal-like tumors demonstrated no additional effect of combination therapy. Vascular characterization demonstrated a total inhibition of endothelial cell proliferation (pMVD) and reduction in mean vascular density (MVD) in the basal-like tumors three days after bevacizumab treatment, not seen in the luminal-like tumors. At day 10, combination treatment reduced pMVD and MVD in both tumors, however only MVD lasted to the end of the experiment and in the basal-like tumors. Analysis of kinase activity in the basal-like tumors after monotherapy demonstrated an early (day 3) increase in the phosphorylation of several targets, followed by a reduction at day 10. Furthermore, the most effective treatment in vivo was accompanied with increased phosphorylation of growth control -and proangiogenic kinase substrates, like PLCγ1, EGFR, PDGFRβ, VEGFR2, and MAP kinases. Early inhibition of vascular proliferation and upregulation of specific signaling pathways, as described above, may therefore indicate important markers for response. Such markers may also be of value in patient stratification, for the prediction of treatment effect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-299. doi:10.1158/1538-7445.AM2011-LB-299