DNA DOUBLE STRAND REPAIR PROTEINS AND CANCER DIAGNOSIS

DNA 双链修复蛋白与癌症诊断

• 批准号: 6143062
• 负责人: ROBERT J CHRISTY
• 金额: $ 10万
• 依托单位: GENETEX, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-07 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6143062
• 关键词: DNA damage; DNA repair; biomarker; diagnosis design /evaluation; gene expression; gene targeting; immunoprecipitation; monoclonal antibody; neoplasm /cancer diagnosis; neoplasm /cancer genetics; polymerase chain reaction; protein localization; protein structure function; tumor suppressor genes; western blottings

Genomic instability, a hallmark of cancer cells, cart be produced by cytotoxic drugs and ionizing radiation.and occurs for multiple reasons, including loss of cell cycle checkpoint control or defects in the DNA damage repair machinery. The lack of maintenance of genomic integrity provides a mechanism for both tumor progression and tumor heterogeneity. A major process involved in repairing DNA damage and preventing cancer formation due to chromosomal fragmentation, translocations or deletions is the double strand break (DSB) repair pathway. We believe that the alteration in expression of tumor suppressor genes involved in DSB and genes directly involved with DNA double strand break repair may provide information on how to treat a particular cancer. We hypothesize that the expression levels and/or cellular localization of proteins involved in double strand break repair are clinically important biological features that lead to improved treatment response to cytotoxic chemotherapy and better outcome in breast and other cancers. To test this, we will generate the biochemical reagents to enable us and other researchers to determine if the expression or production of specific proteins involved in DSB are altered by chemotherapeutic drugs in cancer cells. This information will facilitate the determination of unique prognostic and predictive indicators and help clinicians decide whether a given patient should receive a specific chemotherapy. PROPOSED COMMERCIAL APPLICATIONS: Antibodies against these proteins involved in DNA repair will be useful in dissecting and understanding the pathways involved in the cellular response to DNA damage. We can anticipate that one or more of these proteins may be important in specific cancers, including prostrate, colon and breast cancer and the resulting antibodies will be useful tools in the future diagnosis of these diseases.

基因组不稳定性，癌细胞的标志，通过细胞毒性药物产生和电离辐射产生。出于多种原因发生，包括失去细胞周期检查点控制或DNA损伤修复机械中缺陷。缺乏基因组完整性的维持为肿瘤进展和肿瘤异质性提供了一种机制。涉及修复DNA损伤并防止染色体碎片，易位或缺失引起的癌症形成的主要过程是双链断裂（DSB）修复途径。我们认为，涉及DSB的肿瘤抑制基因表达的改变以及直接与DNA双链断裂修复有关的基因可以提供有关如何治疗特定癌症的信息。我们假设参与双链断裂修复的蛋白质的表达水平和/或细胞定位是临床上重要的生物学特征，可改善对细胞毒性化学疗法的治疗反应，并在乳腺癌和其他癌症中更好地预后。 为了测试这一点，我们将生成生化试剂，以使我们和其他研究人员能够确定与DSB有关的特定蛋白的表达或产生是否会因癌细胞中的化学治疗药物而改变。 这些信息将促进确定独特的预后和预测指标，并帮助临床医生决定是否应接受特定的化学疗法。拟议的商业应用：针对DNA修复的这些蛋白质的抗体将有助于解剖和理解与DNA损伤涉及的途径。我们可以预料，这些蛋白质中的一种或多种可能在特定的癌症中很重要，包括俯卧，结肠和乳腺癌，所得抗体将是对这些疾病的未来诊断的有用工具。