Aurora Kinase as a Therapeutic Target in Cancer

描述（由申请人提供）：胰腺癌是第四大 在美国死于癌症的原因。它的存活率是 所有的恶性肿瘤数据库新目标的发现 存在于胰腺癌细胞中是至关重要的， 预防和治疗胰腺癌。在本提案中，我们 描述了一个新的目标，极光激酶，染色体分离的关键调节器 存在于胰腺癌细胞中，通过额外的工作，我们认为可以 用于为患者开发新的治疗方法。极光激酶是 丝氨酸/苏氨酸激酶超家族的成员。他们有着 能力（是致癌基因），并存在于各种人类肿瘤中 （尤其是胰腺癌）。在初步工作中，我们记录了 极光激酶在所有胰腺癌细胞系中上调，但在 正常胰腺导管细胞此外，它在胰腺癌中上调， 直接从病人身上取下的癌症，在一些病人的 肿瘤的这一初步信息使极光激酶成为一个非常有吸引力的新的 胰腺癌的靶点。该提案的具体目标是：1.到 进一步验证极光激酶作为胰腺癌的靶点。的假设 极光激酶是胰腺癌患者的重要靶点， 细胞2.设计干扰极光激酶活性的药物。 假设是可以找到可以选择性抑制 激酶。将使用两种特殊技术来产生主要代理人。如将 从建议书中可以看出，我们有了一个开始设计工作的线索。3.到 对与极光相互作用的试剂进行体外和体内测试 激酶，以选择将成为临床试验候选药物， 晚期胰腺癌患者。假设我们可以 发现极光激酶的抑制剂，其可以抑制生长（或引起 细胞凋亡）的胰腺癌细胞的体外和体内研究。极光激酶 有相当大的潜力成为患者治疗的一个非常重要的靶点， 胰腺癌，可以设计新的治疗方法， 开发

DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth leading cause of death from cancer in the United States. It has the worst survival of any malignancy followed in the S.E.E.R. database. The discovery of new targets present in pancreatic cancer cells is critically important, both for the prevention and for the treatment of pancreatic cancer. In this proposal, we describe a new target, aurora kinase, a key regulator of chromosome segregation present in pancreatic cancer cells which, with additional work, we feel can be used to develop new therapies for patients with the disease. Aurora kinases are members of the serine/threonine kinase superfamily. They have transforming capacities (are oncogenes) and are present in a variety of human tumors (particularly pancreatic cancer). In preliminary work, we have documented that aurora kinase is upregulated in all pancreatic cancer cell lines but not in normal pancreatic ductal cells. In addition, it is upregulated in pancreatic cancer taken directly from patients and is also amplified in some patients' tumors. This preliminary information makes aurora kinase a very attractive new target in pancreatic cancer. The specific aims of this proposal are: 1. To further validate aurora kinase as a target in pancreatic cancer. The hypothesis is that aurora kinase is an important target in patients' pancreatic cancer cells. 2. To design agents which interfere with the activity of aurora kinase. The hypothesis is that agents can be found which can selectively inhibit the kinase. Two special techniques will be used to generate lead agents. As will be seen in the proposal, we have a lead from which to begin our design work. 3. To perform in vitro and in vivo testing of agents which interact with aurora kinase to select an agent which would be a candidate for clinical trials in patients with advanced pancreatic cancer. The hypothesis is that we can discover inhibitors of aurora kinase which can inhibit growth (or cause apoptosis) of pancreatic cancer cells both in vitro and in vivo. Aurora kinase has considerable potential to be a very important target in patients' pancreatic cancers, against which new therapeutics can be designed and developed.