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（由申请人提供）：I期。在癌症的治疗中，放射疗法受到周围正常组织（例如肺或粘膜）的耐受性的限制。到目前为止，还没有化合物可以保护正常组织而不降低肿瘤对放射治疗的反应。该项目的总体目标是开发一种新的放射治疗癌症的方法，基于最近发现的新型合成催化SOD模拟化合物的辐射防护作用。这些化合物在某些条件下也可以独立地抑制肿瘤生长。在该SBIR应用的第1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。拟议的研究将专门研究一种选定的化合物，为旨在提高放射治疗疗效的人体研究做准备。目标是增加正常组织对放射治疗的耐受性，并保持或增加净抗肿瘤作用。将使用完善的功能、放射学和组织病理学终点来评估该化合物在大鼠和仓鼠辐射诱导损伤模型中的辐射防护作用背后的可能机制。将研究辐射诱导的粘膜炎和辐射诱导的肺纤维化的模型。将通过使用标准肿瘤生长延迟测定来评价单独给予或与放射疗法组合给予的所选SOD模拟物的抗肿瘤作用。这种利用具有抗肿瘤和辐射防护特性的单一化合物与放射治疗相结合的新策略可能会改善患者的生存率，同时降低并发症的风险。SOD模拟物的独立肿瘤生长抑制潜力将是额外的益处。