Anti-angiogenic & anti-tumor drug for human glioma

目前正在研究许多癌症治疗的新方法，包括基因疗法、免疫疗法以及传统疗法和新疗法的组合。通过针对癌细胞的增殖和扩散中的多个事件，可以提高治疗的有效性，避免对治疗的耐药性。由于SF/HGF可以通过对肿瘤细胞以及肿瘤血管内皮细胞的多方面作用促进肿瘤生长，因此它提供了一个很好的治疗靶点。许多胶质瘤细胞系含有SF/HGF的受体c-met，因此有望成为SH/HGF拮抗的靶点。此外，SF/HGF拮抗剂还可以防止内皮细胞的增殖，内皮细胞比肿瘤细胞更容易接近，可能是没有明显副作用的特定靶点，由于其遗传稳定性，不太可能产生耐药性，并且可以针对不同的肿瘤类型。目前的拨款建议使用通过相位显示和计算机模拟设计的小分子来抑制分散因子/肝细胞生长因子(SF/HGF)的血管生成和生长活性的新方法，以抑制肿瘤生长和提高化疗的有效性。在这些研究中，我们将继续开发我们已经确定的具有SF/HGF拮抗活性的化合物，并进行定向筛选过程以寻找更多的SF/HGF拮抗剂，目标是提高疗效和最小的毒性。拟议的商业应用：第一阶段和第二阶段项目旨在提供关键的临床前数据，以支持SF/HGF和用于治疗性血管生成的模拟分子的监管申报和临床试验的启动。该公司预计将与制药行业合作伙伴进行临床开发和商业化。

Numerous novel approaches to cancer therapy are currently being examined including gene therapy, immunotherapy and combinations of traditional and novel therapies. By targeting multiple events in the proliferation and spread of cancer cells the effectiveness of treatments may be improved and resistance to therapy avoided. Since SF/HGF may promote tumor growth through multiple actions both on cancer cells as well as endothelial cells in the vasculature supplying the tumors., it provides an excellent therapeutic target. Many glioma cell lines contain c-met, the receptor for SF/HGF and are therefore promising targets for SH/HGF antagonism. In addition SF/HGF antagonists would also prevent proliferation of endothelial cells which are more easily accessible than tumor cells, may be targeted specifically without significant side effects, are not likely to develop drug resistance because of their genetic stability and can be targeted for different tumor types. The current grant proposes to use the novel approach of inhibition of the angiogenic and growth activities of scatter factor/hepatocyte growth factor (SF/HGF) using small molecules designed by phase display and computer modeling in order to inhibit cancer growth and enhance the effectiveness of chemotherapy. In these studies we will continue development of a compound we have already identified with SF/HGF antagonistic activity and pursue a directed screening process to identify additional SF/HGF antagonists with the goal of improved efficacy and minimal toxicity. PROPOSED COMMERCIAL APPLICATIONS: The Phase I and Phase II projects are designed to provide the key pre- clinical data to support regulatory filing and launch of clinical trials of SF/HGF and mimetic molecules for therapeutic angiogenesis. The company expects to pursue clinical development and commercialization with a pharmaceutical industry partner.