INDUCTION AND SUPPRESSION OF ANGIOGENESIS

血管生成，即从原有血管细胞形成新的血管，对肿瘤的进展生长和转移是必不可少的。旨在抑制肿瘤血管生成的治疗方法在癌症治疗中大有可为。我们已经提出(并在第一阶段提出了证据)，一种特定的最近表征的哺乳动物因子是调节肿瘤血管生成开始和发展的极佳候选者。第二阶段的具体目标是：1)确定阻断该因子的血管生成活性是否抑制肿瘤生长和体内血管生成；2)将该因子用于标准化的体外和体内试验，以分别促进大规模筛选和随后的二次小规模筛选，以确定该因子的阻滞剂作为候选抗癌剂；3)测试-示范该筛选方案，以确定此类候选抗癌剂。这些目标的实现将确立开发该因子作为发现新型抗癌药物的商品化试剂的有效性和可行性，并将发现阻断该因子血管生成活性的潜在抗癌药物。拟议的商业应用：癌症是美国第二大死亡原因，其医疗保健成本远远超过1000亿美元。实体肿瘤占癌症的大多数，每年折磨着300多万人，并导致50多万人死亡。抗血管生成抗癌药的医疗保健市场非常重要，因为传统的化疗选择耐药癌细胞，并对正常组织造成显著的毒性。

Angiogenesis, formation of new blood vessels from cells of preexisting vessels, is essential for progressive tumor growth and metastasis. Therapies aimed at inhibiting tumor angiogenesis hold great promise in cancer treatment. We have proposed (and presented evidence in Phase I) that a specific recently characterized mammalian factor is an excellent candidate for a regulator of the initiation and progression of tumor angiogenesis. The specific aims of Phase II are: 1) the determination of whether blocking the angiogenic activity of this factor inhibits tumor growth and angiogenesis in vivo; 2) the use of this factor in the development of standardized ex vivo and in vivo assays to facilitate, respectively, large-scale screening and subsequent secondary small-scale screening to identify blockers of this factor as candidate anti-cancer agents; 3) the test-demonstration of this screening protocol to identify such candidate anti-cancer agents. Fulfillment of these aims would establish the validity and feasibility of developing this factor as a marketable reagent to discover novel anti-cancer agents, and also would identify potential anti-cancer agents that block the angiogenic activity of this factor. PROPOSED COMMERCIAL APPLICATION: Cancer is the second leading cause of mortality in the U.S., and its health care costs are well over $100 billion. Solid tumors comprise the majority of cancers, afflict over 3 million people, and cause over a half million deaths annually. The health care market for anti-angiogenesis anti-cancer agents is very significant because conventional chemotherapy selects for resistant cancer cells, and causes significant toxicity to normal tissue.