Radiation Protection Cancer Therapy with an SOD Mimetic

描述(申请人提供)：第一阶段。在癌症的治疗中，放射治疗受到周围正常组织，如肺或粘膜的耐受性的限制。到目前为止，还没有化合物可以在不降低肿瘤对放射治疗的反应的情况下保护正常组织。该项目的总体目标是开发一种新的癌症放射治疗方法，基于最近发现的新的合成催化超氧化物歧化酶模拟化合物的辐射防护作用。在某些条件下，这些化合物也可能独立地抑制肿瘤生长。在这项SBIR应用的第一阶段，特定的超氧化物歧化酶模拟物将在人类癌症放射治疗的动物模型中证明有效。这项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效果的人体研究做准备。其目标是既增加正常组织对放射治疗的耐受性，又保留或增加净抗肿瘤效果。已确定的功能、放射学和组织病理学终点将用于评估该化合物在辐射诱导损伤的大鼠和仓鼠模型中的辐射防护作用背后的可能机制。辐射诱导的粘膜炎和辐射诱导的肺纤维化的模型将被研究。选择的超氧化物歧化酶模拟物单独给予或联合放射治疗的抗肿瘤效果将通过标准的肿瘤生长延迟试验进行评估。这一新策略利用一种同时具有抗肿瘤和辐射防护性能的化合物与放射治疗相结合，可以改善患者的存活率，同时降低并发症的风险。通过超氧化物歧化酶模拟物独立抑制肿瘤生长的潜力将是一个额外的好处。

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.