Therapeutic Micro RNA Strategies for Ovarian Cancer

上皮性卵巢癌(EOC)是妇科恶性肿瘤相关死亡的最常见原因。 女人。尽管以铂/紫杉烷为基础的化疗的进展提高了存活率， 患者通常会在最初治疗后两年内复发，并对 心理治疗。因此，开发新的治疗方法是当务之急。分子靶向药物前景看好 作为独立的治疗药物或化疗反应调节剂，并可能对 平等机会委员会对女性面貌的改善。MicroRNAs(MiRNAs)是-22个核苷酸非编码的 RNA，以序列特异性的方式负向调节基因表达。我们已经生成了 首次有证据表明miRNAs在基因组中表现出高频变化，并且它们的表达显著 在卵巢癌方面放松管制。这有力地表明miRNAs参与了启动和 这种疾病的发展。事实上，我们的初步研究表明，miRNA是一类新的 极具潜力的生物标志物在卵巢癌早期发现、诊断和治疗反应中的应用 预测。我们假设miRNAs在预测性和可预测性的进化中可能起到两个作用 EoC的治疗策略。首先，miRNAs有可能准确地预测反应 以及对特定化疗的抗药性。第二，从长远来看，可能更令人兴奋的是 选择mlRNA作为治疗工具和/或化疗反应的可能性 将为EoC提供新的治疗机会的修饰剂。我们提出了以下具体目标 为卵巢癌开发基于miRNA的治疗工具。具体目标1：确定功能和治疗 精选miRNAs在体外的潜力。具体目标2：确定选定的miRNAs的治疗潜力 活着。具体目标3：在L/11期试验中，开发一个或多个针对特定mlRNA的构建物。 具体目标4：评估miRNAs对给定化疗的反应和耐药性的预测价值。 相关性(请参阅说明)： 卵巢上皮癌是女性妇科癌症相关死亡的最常见原因。 MiRNAs是一种小的非编码RNAs，它负向调节特定序列中的基因表达 举止。我们将对卵巢癌中的miRNA进行详细的研究，这还没有进行到 日期，意在(I)发现卵巢癌临床治疗或预后的新生物标志物；(Ii) 发现新的和重要的治疗靶点。

Epithelial ovarian cancer (EOC) is the most frequent cause of gynecologic malignancy-related mortality in women. Although advances in platinum/taxane-based chemotherapy have resulted in improved survival, patients typically experience disease relapse within 2 years of the initial treatment and develop resistance to therapy. Therefore, development of new therapies is a high priority. Molecular targeted drugs hold promise as independent therapeutic agents or chemotherapy response modifiers and could contribute substantial improvements to the outlook of women with EOC. microRNAs (miRNAs) are -22 nucleotide non-coding RNAs, which negatively regulate gene expression in a sequence-specific manner. We have generated the first evidence that miRNAs exhibit genomic alterations at high frequency and their expression is remarkably deregulated in ovarian cancer. This strongly suggests that miRNAs are involved in the initiation and progression of this disease. Indeed, our preliminary studies demonstrate that miRNA is a new class of novel biomarker with strong potential application to EOC in eariy detection, diagnosis and therapeutic response prediction. We hypothesize that miRNAs might serve two roles in the evolution of predictive and therapeutic strategies in EOC. First, it is possible that miRNAs might accurately predict response and resistance to a given chemotherapy. Second, and potentially more exciting in the long term, is the potential that selected mlRNA's might serve as therapeutic tools and/or chemotherapy response modifiers that will offer novel therapeutic opportunities for EOC. We propose the following specific aims to develop miRNA-based therapeutic tools for EOC. Specific Aim 1: Determine the function and therapeutic potential of select miRNAs in vitro. Specific Aim 2: Determine the therapeutic potential of select miRNAs in vivo. Specific Aim 3: Develop one or more constructs directed to specific mlRNA's in Phase l/ll trials. Specific Aim 4: Evaluate the predictive value of miRNAs response and resistance to a given chemotherapy. RELEVANCE (See Instructions): Epithelial ovarian cancer is the most frequent cause of gynecologic cancer-related mortality in women. miRNAs are small non-coding RNAs, which negatively regulate gene expression in a sequence-specific manner. We will conduct a detailed study of miRNA in ovarian cancer, which has not been carried out to date, with the intent to (i) discover new biomarkers for ovarian cancer clinical management or prognosis; (ii) discover novel and important therapeutic targets.