ANTI-ANGIOGENIC MIMETICS FOR CANCER THERAPY

描述：（申请人的描述） 血管生成，即新血管的形成，是进行性 肿瘤生长和转移。 旨在抑制肿瘤血管生成的疗法 (and通过营养饥饿缩小肿瘤）在 癌症治疗，因为他们避免了两个主要问题， 标准化疗，即，化疗耐药细胞的最终生长 肿瘤和由化疗引起的使人衰弱的全身副作用。 特别是，生物制剂的合理设计， 抑制体内促肿瘤因子的血管生成活性， 这可能是产生这种新型治疗剂的极好方法。 的 该提案第一阶段的具体目标是：1）产生和纯化可能的 可以特异性抑制肿瘤的候选生物制剂 特定血管生成因子的血管生成和肿瘤促进活性 它强烈暗示是肿瘤生长的重要调节剂，以及2） 为了在活体动物模型中筛选这些药剂，以确定它们阻断 靶向因子的血管生成活性。 确定为抑制剂的药物 靶向因子的血管生成活性将在第二阶段进行测试， 它们抑制和/或消退肿瘤生长促进活性的能力 目标因素，以及那些能够这样做的将被开发 进一步作为临床抗癌剂。 拟定商业应用： 癌症是美国第二大死亡原因，它的医疗费用 超过1000亿美元。 实体瘤占癌症的大多数，折磨着超过300万人。 每年造成50多万人死亡。 医疗保健市场的抗- 血管生成抗癌剂是非常重要的，因为常规化疗 选择耐药的癌细胞，并对正常组织产生显著毒性。

DESCRIPTION: (Applicant's Description) Angiogenesis, formation of new blood vessels, is essential for progressive tumor growth and metastasis. Therapies aimed at inhibiting tumor angiogenesis (and shrinking tumors through nutrient starvation) hold great promise in cancer treatment, because they avoid two of the major problems associated with standard chemotherapy, i.e., the eventual growth of chemotherapy-resistant tumors and the debilitating systemic side effects engendered by chemotherapy. In particular, the rational design of biological agents that specifically suppress the angiogenic activity of tumor-promoting factors in the body is potentially an excellent means of creating such novel therapeutic agents. The specific aims of phase I of this proposal are 1) to generate and purify likely candidate biological agents that may specifically suppress the tumor angiogenic and tumor promoting activities of a particular angiogenic factor that is strongly implicated as an essential regulator of tumor growth, and 2) to screen these agents in a live animal model for their ability to block the angiogenic activity of the targeted factor. Agents identified as suppressors of the targeted factor's angiogenic activity would be tested in Phase II for their ability to suppress and/or regress the tumor growth-promoting activity of the targeted factor, and those that are able to do so would be developed further as clinical anti-cancer agents. 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.