Radiation Protection Cancer Therapy with an SOD Mimetic

使用 SOD 模拟物进行辐射防护癌症治疗

• 批准号: 6878074
• 负责人: ELAINE ALEXANDER
• 金额: $ 37.5万
• 依托单位: AEOLUS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-14 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6878074
• 关键词: biomimetics; biotherapeutic agent; drug screening /evaluation; hamsters; laboratory rat; metalloporphyrins; neoplasm /cancer radiation therapy; oral mucosa; pulmonary fibrosis /granuloma; radiation therapy dosage; radioprotective agents; superoxide dismutase; topical drug application

DESCRIPTION (provided by applicant): Phase I. In the treatment of cancer, radiation therapy has been limited by the tolerance of the surrounding normal tissues, such as lung or mucosa. Until now, there have been no compounds available that protect the normal tissues without reducing the tumor response to radiation therapy. The overall goal of this project is to develop a new approach to radiation therapy for cancer, based on the recently discovered radioprotective effects of novel synthetic catalytic SOD mimetic compounds. These compounds may also independently inhibit tumor growth under certain conditions. In Phase 1 of this SBIR application specific SOD mimetics will have demonstrated effectiveness in animal models of radiation therapy of human cancers. The proposed study will specifically research a selected compound in preparation for human studies directed at enhancing the efficacy of radiation therapy. The goal is to both increase tolerance of normal tissues to radiation therapy and retain or increase the net anti-tumor effects. Well-established functional, radiographic and histopathologic end-points will be used to assess possible mechanisms behind this compound's radioprotective effect in rat and hamster models of radiation-induced injury. Models of both radiation-induced mucositis and radiation-induced lung fibrosis will be studied. The antitumor effect of the selected SOD mimetic given alone or in combination with radiation therapy will be evaluated by using standard tumor growth delay assays. This new strategy of utilizing a single compound with both anti-tumor and radioprotective properties in combination with radiotherapy could result in an improvement in patient survival with a concomitant reduction in the risk of complications. The potential of independent tumor growth inhibition by the SOD mimetics would be an additional benefit.

描述（申请人提供）：第一阶段。在癌症的治疗中，放射治疗一直受到周围正常组织（如肺或粘膜）耐受性的限制。到目前为止，还没有一种化合物既能保护正常组织，又能降低肿瘤对放射治疗的反应。该项目的总体目标是基于最近发现的新型合成催化SOD模拟化合物的放射防护作用，开发一种新的癌症放射治疗方法。这些化合物也可能在一定条件下独立抑制肿瘤生长。在SBIR应用的第一阶段，特异性SOD模拟物将在人类癌症放射治疗的动物模型中证明有效性。这项拟议的研究将专门研究一种选定的化合物，为人体研究做准备，旨在提高放射治疗的疗效。目标是增加正常组织对放射治疗的耐受性，同时保持或增加净抗肿瘤效果。已建立的功能、放射学和组织病理学终点将用于评估该化合物在大鼠和仓鼠辐射损伤模型中辐射防护作用的可能机制。将研究辐射性粘膜炎和辐射性肺纤维化的模型。所选择的SOD模拟物单独或与放射治疗联合使用的抗肿瘤效果将通过标准肿瘤生长延迟试验进行评估。这种利用具有抗肿瘤和放射防护特性的单一化合物与放射治疗相结合的新策略可以改善患者的生存，同时降低并发症的风险。SOD模拟物独立抑制肿瘤生长的潜力将是一个额外的好处。