Bithionol As An Inhibitor Of Tumor Angiogenesis

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Tumor progression depends on angiogenesis. The clinical successes in recent years have demonstrated that antiangiogenic agents can be developed as effective treatment for cancer patients. However, the resistance to the current FDA approved antiangiogenic therapies is emerging, which presents challenges in cancer research and urgent needs for novel angiogenesis inhibitors with different mechanisms of drug actions to overcome the resistance. In our previous studies, we have identified a small molecule bithionol as a potential antiangiogenic agent through a chemical diversity library screening with a cell-based angiogenesis assay. Bithionol is a FDA approved and current clinically used anthelmintics, which has been found to directly inhibit activity of autotaxin, a secreted enzyme that catalyzes lysophosphatidic acid (LPA) production. LPA, as a lipid signaling molecule, is a potent angiogenic and cancer cell motility stimulating factor. Therefore, autotaxin plays important role in tumor angiogenesis and metastasis and has been recently identified as an attractive angiogenesis and cancer target. Our recent studies have shown that autotaxin is expressed at high levels in human endothelial and number of human cancer cell lines. Bithionol has demonstrated inhibitory activities against human endothelial cell proliferation, migration, and tube-formation as the three key cellular steps in angiogenesis process. The effect of bithionol on inhibition of tumor angiogenesis was also evaluated with an ex vivo xenograft chicken embryo chorioallantoic membrane (xenograft-CAM) model system. Bithionol is able to inhibit tumor-induced new blood vessel formation in a dose dependent manner and has demonstrated an additive inhibitory activity when it is applied in combination with Sutent, a current clinically used antiangiogenic drug. The results of this research suggest that bithionol provide a unique promising opportunity in developing new combinational treatment to increase the anticancer efficacy and minimize the resistance in cancer patients. 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 4265. doi:10.1158/1538-7445.AM2011-4265