Abstract B7: TSU-68 suppresses the progression of malignant pleural mesothelioma cells in SCID mice by inhibiting angiogenesis

Abstract

Abstract Background: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm, for which the therapeutic options are limited. Pemetrexed combined with cisplatin, which has been approved, still has poor overall outcome. Molecular targeted therapies represent a promising strategy for overcoming limitation in therapy of malignant neoplasm including MPM. TSU-68 (SU6668), a tyrosine kinase inhibitor targeting VEGFR2, PDGFRβ and FGFR1 can inhibit the growth of various tumors. However, the efficacy of TSU-68 on MPM has not been investigated. Purpose: Investigate the therapeutic efficacy of TSU-68 on the progression of human MPM cells in an orthotopical implantation model. Method: Y-MESO-14 cells (expressing high level of VEGF and low level of bFGF) and MSTO-211H cells (expressing low level of VEGF and high level of bFGF) were orthotopically inoculated into thoracic cavities of SCID mice. From day 7 after inoculation, mice were treated with either TSU-68 (200mg/kg/day) or vehicle for two weeks. At the end of treatment, mice were sacrificed for analyzing the characteristics of thoracic tumors and pleural effusion. Result: In both cells, TSU-68 inhibited the tumor size, pleural effusion volume and vessel density in the tumor compared to control group. Furthermore, TSU-68 inhibited the proliferation of endothelial cells stimulated by VEGF, bFGF, or supernatant of MPM cell culture media in vitro. Conclusion: TSU-68 has anti-tumor activity for MPM progression. via inhibiting angiogenesis These findings suggest that TSU-68 may be clinically useful to improve the treatment outcome of MPM. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B7.