Prevention of erectile dysfunction following prostate cancer radiotherapy

描述(由申请人提供)： 这项建议的目的是评估BIO 300作为预防和/或减轻前列腺癌放射治疗(RT)后常见的勃起功能障碍(ED)的有效疗法。前列腺癌是美国男性中最常见的癌症。大约一半的前列腺癌患者将接受放射治疗作为治疗的一部分。尽管5年存活率很高(99.2%)，但接受RT治疗的男性中约有一半会在5年内发展为ED。辐射诱发的勃起功能障碍仍然是一个未得到满足的医疗需求，严重影响癌症幸存者，特别是年轻男性的性健康相关生活质量。值得注意的是，可能的性功能丧失在前列腺癌男性的治疗相关决定中发挥着重要作用。人文公司正在开发BIO 300口服混悬剂，以治疗急性辐射暴露(DEARE)的延迟效应，包括辐射引起的肺炎和纤维化。BIO 300具有显著的辐射防护作用，这与其强大的抗氧化和抗炎特性以及对细胞周期分裂的影响有关。一个强有力的科学基础表明，炎症和氧化应激在RT诱导的ED的发生发展中起关键作用。BIO 300的关键生物靶点包括氧化还原信号、炎症途径和氧化应激途径。在暴露于致命剂量胸部照射的小鼠中，BIO 300被证明在辐射后24小时开始治疗并仅持续14天时，可以减轻正常组织损伤并提高存活率。这些数据支持BIO 300在预防RT诱导的ED方面同样有效的假设。这项提议的目的是为这一假说提供科学支持。第一个目标 将使用客观的生理终点和氧化应激标志物的免疫染色，在RT诱导的ED模型中确定BIO 300的治疗效果。第二个目标将确定BIO 300在前列腺癌啮齿动物模型中对肿瘤发展的影响。为了实现这一目标，将比较接受BIO 300治疗的动物和未接受BIO 300治疗的动物的RT诱导的肿瘤生长延迟和肿瘤病理。这一目标的目的是确保BIO 300不会对针对肿瘤的RT产生负面干扰。事实上，根据已发表的文献，BIO 300联合RT有望增强肿瘤生长延迟。如果成功，这些研究将推动BIO 300作为RT诱导的ED的治疗选择的发展，并将对未来患有ED的癌症幸存者以及被诊断为前列腺癌的患者产生积极影响。

DESCRIPTION (provided by applicant): The aim of this proposal is to evaluate BIO 300 as an effective therapy to prevent and/or mitigate the erectile dysfunction (ED) that is commonly observed following radiotherapy (RT) for prostate cancer. Prostate cancer is the most common cancer among men in the United States. Approximately half of prostate cancer patients will undergo RT as a part of their treatment. Even though 5 year survival rates are high (>99.2%), about half of the men who receive RT will develop ED within 5 years. Radiation-induced ED remains an unmet medical need that severely impacts the sexual health-related quality of life of cancer survivors, especially younger men. Significantly, possible loss of sexual function plays an important role in treatment-related decisions for men with prostate cancer. Humanetics Corporation is developing BIO 300 oral suspension to treat the delayed effects of acute radiation exposure (DEARE), including radiation-induced pneumonitis and fibrosis. BIO 300 has substantial radioprotective effects linked to its strong antioxidant and anti-inflammatory properties, and its effects on cell cycle division. A strong scientific rationale suggests that inflammation and oxidative stress are critica to development of RT-induced ED. Key biological targets of BIO 300 include redox signaling, inflammatory pathways, and oxidative stress pathways. In mice exposed to a lethal dose of thoracic irradiation, BIO 300 was shown to mitigate normal tissue injury and improve survival when treatment was started 24 hours after radiation and continued for just 14 days. These data support the hypothesis that BIO 300 will be equally effective at preventing RT-induced ED. The aims of this proposal are designed to provide scientific support for this hypothesis. The first aim will determine the therapeutic efficacy of BIO 300 in a model of RT-induced ED, using objective physiological endpoints and immunostaining for oxidative stress markers. The second aim will determine the effect of BIO 300 on tumor development in a rodent model of prostate cancer. Toward that goal, the RT-induced tumor growth delay and tumor pathology will be compared for animals treated with BIO 300 vs. those that do not receive BIO 300 therapy. The goal of this aim is to ensure that BIO 300 does not negatively interfere with RT directed at tumors. In actuality, based on a published literature, BIO 300 in combination with RT is expected to enhance tumor growth delay. If successful, these studies will advance the development of BIO 300 as a treatment option for RT-induced ED, and will positively impact cancer survivors living with ED as well as patients diagnosed with prostate cancer in the future.