Translational Research Studies in Clinical Trials of Novel Therapeutics for Sarco

描述（由申请人提供）：20%最罕见的癌症占美国癌症死亡人数的35%左右。因此，更好地了解这些罕见肿瘤的性质符合公共卫生的最佳利益。我们研究肉瘤，一种罕见的结缔组织癌症：骨骼、肌肉、脂肪、软骨和其他将我们联系在一起的组织。这些癌症大多发生在儿童、青少年和年轻人身上，尽管不同的形式会影响不同的年龄组。总的来说，肉瘤占美国所有癌症的比例不到1%。然而，由于它们可以起源于许多不同的组织，因此有70种或更多的肉瘤亚型。我们感兴趣的是为患有这些罕见癌症的人找到新的治疗方法，他们没有从更常见的癌症研究中受益。我们已经确定了两种新的药物组合，可能对肉瘤患者有用。其中第一种是A12，一种“胰岛素样生长因子1受体”抑制剂，以及替西莫司，一种mTOR抑制剂。第二种是Hh （hedgehog）信号阻滞剂GDC-0449，在一项针对复发性肉瘤患者的新研究中，我们正在将其与γ分泌酶阻滞剂（RO4929097） （Notch通路）联合使用。我们正在寻求资金来进行这项多中心研究，重点是在这两项研究中对患者进行活检，以寻找阻断这些不同途径的生物学相关性。这些活组织检查将帮助我们确定是否会从这种治疗中受益。我们还将使用我们最近开发的一个名为StudyTracker的软件工具，从多个参与GDC-0449/RO4929097 I-II期研究的中心收集数据。有了这些信息，我们将能够使用肿瘤测试来确保正确的人接受正确的药物治疗，并有最大的机会从治疗中获得良好的结果。如果没有这样的测试，临床试验就会沦为“扔飞镖”——有些人可能会受益，但我们不明白为什么。这种方法应该会导致新的和有效的手段来治疗肉瘤患者，也可能影响更常见的癌症患者。

DESCRIPTION (provided by applicant): The 20% rarest cancers account for approximately 35% of the deaths from cancer in the United States. As a result, a better understanding of the nature of these rare tumors is in the public health's best interest. We study sarcomas, rare cancers of connective tissue: bone, muscle, fat, cartilage, and the other tissues that hold us together. These are cancers that occur disproportionately in children, teens, and young adults, although different forms affect different age groups. In all, sarcomas account for less than 1% of all cancer in the United States. However, since they can arise from so many different tissues, there are 70 or more sarcoma subtypes. We are interested in finding new treatments for the people with these rare cancers, who do not benefit from research on more common cancers. We have identified two new combinations of drugs that may be useful for people with sarcoma. The first of these is A12, an "insulin-like growth factor 1 receptor" inhibitor, and temsirolimus, an mTOR inhibitor. The second is a blocker of Hh (hedgehog) signaling, GDC-0449, which we are combining with a blocker of gamma secretase (RO4929097) [Notch pathway] in a novel study for people with recurrent sarcomas. We are seeking funding to perform this multi-center study, focusing on biopsies from patients on these two studies for biological correlates of blockade of these various pathways. These biopsies will help us determine would or would not benefit from such therapy. We will also use a software tool we have recently developed, called StudyTracker, to collect the data from the multiple participating centers on the GDC-0449/RO4929097 phase I-II study. With this information, we will be able to use tests of tumors to insure that the right person is receiving the right medication, with the best chance of getting a good result from that treatment. Without such testing, clinical trials are reduced to "throwing darts"-some people could benefit, but we will not understand why. This approach should lead to new and efficient means to treat patients with sarcomas and may also impact patients with more common cancers. PUBLIC HEALTH RELEVANCE: This is a project to support correlative studies for two multicenter clinical trials of new drugs for patients with sarcomas. These novel approaches will improve the treatment options for this underserved group of patients with this rare family of cancers