Aurora Kinase as a Therapeutic Target in Cancer

极光激酶作为癌症治疗靶点

• 批准号: 7124244
• 负责人: DANIEL D VON HOFF
• 金额: $ 32.52万
• 依托单位: TRANSLATIONAL GENOMICS RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7124244
• 关键词: antineoplastics; cell line; chromosome movement; drug design /synthesis /production; drug screening /evaluation; enzyme induction /repression; enzyme inhibitors; oncogenes; pancreas neoplasms; protein kinase

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.

描述（由申请人提供）：胰腺癌是第四大癌症 美国癌症死亡原因。它的生存最差 S.E.E.R. 中发现的任何恶性肿瘤数据库。新目标的发现 存在于胰腺癌细胞中至关重要，无论是对于 用于预防和治疗胰腺癌。在这个提案中，我们 描述了一个新的靶标，极光激酶，染色体分离的关键调节因子 存在于胰腺癌细胞中，通过额外的工作，我们认为可以 用于为患有该疾病的患者开发新疗法。极光激酶是 丝氨酸/苏氨酸激酶超家族的成员。他们有转型 能力（癌基因）并存在于多种人类肿瘤中 （特别是胰腺癌）。在前期工作中，我们已经记录了 极光激酶在所有胰腺癌细胞系中均上调，但在 正常胰腺导管细胞。此外，它在胰腺中上调 直接取自患者的癌症，在某些患者体内也会被放大 肿瘤。这一初步信息使极光激酶成为一种非常有吸引力的新药物 胰腺癌的目标。本提案的具体目标是： 1. 进一步验证极光激酶作为胰腺癌的靶点。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。 假设可以找到可以选择性抑制 激酶。将使用两种特殊技术来生成主要代理。将会如此 从提案中可以看出，我们已经有了开始设计工作的线索。 3. 到 对与极光相互作用的药物进行体外和体内测试 激酶来选择一种药物，该药物将成为临床试验的候选药物 晚期胰腺癌患者。假设我们可以 发现极光激酶抑制剂，它可以抑制生长（或导致 胰腺癌细胞的体外和体内凋亡）。极光激酶 有很大潜力成为患者的一个非常重要的目标 胰腺癌，可以设计新的治疗方法 发达。