TREATMENT RESPONSE MARKERS IN ADVANCED LARYNGEAL CANCER

晚期喉癌的治疗反应标志物

• 批准号: 6514176
• 负责人: CAROL R. BRADFORD
• 金额: $ 23.43万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514176
• 关键词: BCL2 gene /protein; apoptosis; cell line; cis platinum compound; clinical research; combination cancer therapy; gene expression; gene mutation; genetic markers; human subject; human therapy evaluation; immunocytochemistry; larynx neoplasms; neoplasm /cancer chemotherapy; neoplasm /cancer invasiveness; neoplasm /cancer radiation therapy; outcomes research; p53 gene /protein; prognosis; quality of life; single strand conformation polymorphism; tissue /organ preservation

Description: (adapted from the investigator's abstract) A critical research chemoradiation, and the lack of predictive markers for identifying those likely to respond. Advanced laryngeal cancer is a devastating disease for which better therapies are needed. Surgery is effective in some patients but the surgical defects can be functionally and cosmetically unacceptable and many patients recur after surgery. Thus, the development of predictive markers to select patients for appropriate therapy is needed. Our preliminary results suggest that p53 expression or mutation and expression of the apoptosis-blocking proteins, BCL-2 and BCL-xL, interact to determine responsiveness to chemoradiation. We propose to determine in patients with advanced laryngeal cancer treated on the multi-institutional, randomized Department of Veterans Affairs Laryngeal Cancer Study whether chemotherapy response, organ preservation and/or survival is predicted by p53 overexpression and gene mutation, and we will determine how this is influenced by the expression of BCL-2 and BCL-xL. Our preliminary in vivo and in vitro data support the concept that tumors with mutant p53 are susceptible to cisplatin-based chemotherapy regimens but that those with wild type p53 are resistant. We will test our hypotheses in tumor samples obtained from patients before and after organ-sparing therapy and we will test these hypotheses with in-vitro experiments using cell lines with known p53 and BCL-2/BCL-xL status. The mechanism of cell death (apoptosis-dependent or independent) may determine the efficacy of different interventions and dictate which treatments are appropriate. The information acquired in this work should result in new trials that employ predictive markers to select the most appropriate and effective treatment for advanced laryngeal cancer.

描述：（根据调查员的摘要改编）一项重要研究 化学放疗以及缺乏识别可能的预测标记 回应。晚期喉癌是一种毁灭性疾病 需要疗法。手术对某些患者有效，但是手术 缺陷在功能和外观上可能是不可接受的，许多患者 手术后重复出现。因此，开发预测标记以选择 需要适当治疗的患者。我们的初步结果表明 p53表达或突变和凋亡阻断的表达 蛋白质Bcl-2和Bcl-XL相互作用以确定对 化学放疗。我们建议在患有晚期喉的患者中确定 在多机构的，随机的退伍军人部门治疗的癌症 事务喉癌研究化学疗法反应，器官是否反应 p53过表达和基因预测保存和/或生存 突变，我们将确定这如何受到表达的影响 Bcl-2和Bcl-XL。我们的初步体内和体外数据支持该概念 突变p53的肿瘤易受基于顺铂的化学疗法的影响 方案，但是那些野生型p53的疗法具有抗性。我们将测试我们的 从患者那里获得的肿瘤样本的假设 有器材的疗法，我们将用视野测试这些假设 使用具有已知p53和Bcl-2/bcl-XL状态的细胞系实验。这 细胞死亡的机制（凋亡依赖或独立）可能决定 不同干预措施的功效并决定了哪些治疗方法 合适的。这项工作中获得的信息应导致新试验 使用预测标记来选择最合适和有效的标记 治疗晚期喉癌。