Molecular Targeted Therapy for Retinoblastoma

描述（由申请人提供）：视网膜母细胞瘤是一种儿童期视网膜发育癌症，始于子宫内，在生命的最初几年被诊断出来。这是第三 是继白血病和神经母细胞瘤之后最常见的婴儿癌症。如果不治疗，视网膜母细胞瘤几乎总是致命的，即使有最好的治疗，转移性视网膜母细胞瘤的10%生存率是任何儿科癌症中最差的。在美国，大多数病人都能存活下来，因为癌症在转移之前就被发现了，但挽救病人的生命往往需要手术摘除。这对于患有最晚期形式的双侧视网膜母细胞瘤的儿童来说尤其虚弱;这些患者中约有一半失去至少一只眼睛并且永久性视力受损。这项转化研究的目标是确定新的治疗方法，以挽救视网膜母细胞瘤儿童的视力和转移性进展儿童的生命。我们已经确定了3种新的，令人兴奋的分子靶向疗法，在实验室研究中显示出希望。在本申请中，我们将对这3种药物进行全面的临床前试验。这些研究的结果将用于设计圣裘德儿童研究医院的下一项视网膜母细胞瘤临床试验。因此，成功完成这里提出的目标将直接影响人类健康。该应用的一个独特和创新的方面是我们组建的多学科团队，该团队由眼部肿瘤学家，儿科肿瘤学家，发育神经生物学家，化学家和药理学家组成。该团队在将基础科学发现转化为临床试验，然后与国家和国际社会分享我们的发现以影响全球人类健康的最大变化方面有着良好的记录。该应用的另一个创新方面是我们在视网膜母细胞瘤转化研究和临床前模型开发方面的专业知识，我们已经为这些研究进行了优化和表征。没有其他中心有团队，资源，专业知识或工具可用于执行这里提出的研究，并将最有希望的发现直接转移到临床试验中。

DESCRIPTION (provided by applicant): Retinoblastoma is a childhood cancer of the developing retina that begins in utero and is diagnosed in the first years of life. It is the third most common form of cancer in infants after leukemia and neuroblastoma. If left untreated, retinoblastoma is virtually always fatal, and even with the best treatment, the 10% survival rate for metastatic retinoblastoma is among the worst for any pediatric cancer. In the U.S., most patients survive because the cancer is detected early before it metastasizes, but saving the patient's life often requires surgical enucleation. This is particularly debilitating for children ith the most advanced form of bilateral retinoblastoma; approximately half of those patients lose at least 1 eye and are permanently vision impaired. The goal of this translational research is to identify new treatments to save the vision of children with retinoblastoma and the lives of children with metastatic progression. We have identified 3 novel, exciting molecular-targeted therapies that show promise in laboratory studies. In this application, we will perform comprehensive preclinical testing of these 3 agents. The results from these studies will be used to design the next retinoblastoma clinical trial at St. Jude Children's Research Hospital. Therefore, the successful completion of the Aims presented here will directly impact human health. One unique and innovative aspect of this application is the multidisciplinary team that we have assembled, which is made up of ocular oncologists, pediatric oncologists, developmental neurobiologists, chemists, and pharmacologists. This team has a proven record of moving basic science discoveries into clinical trials and then sharing our findings with the national and international communities to affect the greatest change in global human health. Another innovative aspect of the application is our expertise in retinoblastoma translational research and development of preclinical models, which we have optimized and characterized for these studies. No other center has the team, resources, expertise, or tools available to perform the studies presented here and move the most promising findings directly into a clinical trial.