Expression profiling of renal cell carcinoma utilizing tissue from CALGB 90206

利用 CALGB 90206 组织进行肾细胞癌的表达谱分析

• 批准号: 8312591
• 负责人: HYUNG L KIM
• 金额: $ 34.38万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312591
• 关键词: Angiogenesis Inhibition; Angiogenesis Inhibitors; Antigen Presentation; Archives; Benign; Binding; Biological Assay; Blood Vessels; Cancer Trials Support Unit; Cancer and Leukemia Group B; Candidate Disease Gene; Clear Cell; Clinical; Clinical Trials; Conflict (Psychology); Correlative Study; Defect; Development; Diagnosis; Diagnostic Neoplasm Staging; Disease; Elements; Enrollment; Exposure to; Freezing; Gene Expression; Genes; Genomics; Health; Histocompatibility Antigens Class I; Histopathologic Grade; Hypoxia; Hypoxia-Inducible Factor Pathway; Immune; Immune system; Immunotherapy; Individual; Institution; Interferon-alpha; Interferons; Interleukin-2; Kidney Neoplasms; Link; Literature; Malignant - descriptor; Malignant Neoplasms; Measures; Medical; Messenger RNA; Metastatic Renal Cell Cancer; Microarray Analysis; Modality; Modeling; Molecular; Molecular Profiling; Monoclonal Antibodies; National Cancer Institute; National Cancer Institute of Canada; Nephrectomy; Newly Diagnosed; Outcome; Paraffin; Paraffin Embedding; Pathway interactions; Patients; Phase III Clinical Trials; Primary Neoplasm; Process; Prognostic Marker; Protein Isoforms; Proteins; Proteomics; Publishing; RNA; Radiation; Randomized; Recurrence; Renal Cell Carcinoma; Renal Tissue; Renal carcinoma; Reporting; Resistance; Resources; Reverse Transcription; Science; Solid Neoplasm; Specimen; Technology; Testing; Tissues; Toxic effect; Tumor Biology; Tumor Tissue; Tumor stage; Tyrosine Kinase Inhibitor; Unresectable; VHL mutation; VHL protein; Validation; Vascular Endothelial Growth Factors; antigen processing; base; bevacizumab; chemotherapy; cytokine; effective therapy; immunoregulation; insight; molecular marker; novel marker; outcome forecast; overexpression; patient population; prognostic; randomized trial; repository; response; tool; treatment response; tumor; tumorigenesis

DESCRIPTION (provided by applicant): One third of patients newly diagnosed with renal cell carcinoma (RCC) have metastatic disease. Of patients initially diagnosed with localized RCC, one third will eventually develop metastatic disease despite treatment of the primary tumor. RCC is resistant to conventional chemotherapies and radiation, and generalized cytokine stimulation with interferon-alpha (IFN-1) or interleukin-2 (IL2) represents effective treatment for metastatic RCC. Recent advances in understanding of the disease mechanism have allowed development of more specific treatments. Clear cell RCC is characterized by von Hippel Lindau (VHL) gene mutation, which results in overexpression of downstream gene products such as vascular endothelial growth factor (VEGF). Bevacizumab is a monoclonal antibody that binds and neutralizes all isoforms of the VEGF protein and is being investigated in clinical trials of advanced RCC. CALGB 90206 randomized untreated, metastatic clear cell RCC patients to IFN-1 alone or IFN-1 plus bevacizumab. The study is now closed to enrollment after reaching its target accrual of over 700 patients. As part of the study, pre-treatment paraffin RCC tumor blocks were banked for correlative studies. This large repository of tumor tissue with linked clinical outcome represents a valuable resource for advancing the science of gene expression as a predictive and prognostic tool. We propose using a quantitative, reverse transcription PCR based approach to assess mRNA levels for relevant genes. Gene expression levels are used to develop models for predicting response to treatment, determining prognosis, and assessing the variability in molecular defects associated with RCC. Insights from this analysis will have broad implications across solid tumors and across multiple anti-angiogenic modalities. Treatments for kidney cancer include immune modulation and inhibition of new blood vessel formation. This study uses tumor tissue collected as part of CALGB 90206, a clinical trial for advanced kidney cancer evaluating immunotherapy with or without inhibition of blood vessel formation, to identify molecular markers that can predict survival and response to treatment. PUBLIC HEALTH RELEVANCE: Treatments for kidney cancer include immune modulation and inhibition of new blood vessel formation. This study uses tumor tissue collected as part of CALGB 90206, a clinical trial for advanced kidney cancer evaluating immunotherapy with or without inhibition of blood vessel formation, to identify molecular markers that can predict survival and response to treatment.

描述（由申请人提供）：三分之一的新诊断为肾细胞癌（RCC）的患者有转移性疾病。在最初诊断为局限性RCC的患者中，尽管原发肿瘤得到了治疗，但三分之一的患者最终会发展为转移性疾病。RCC对常规化疗和放疗具有耐药性，而干扰素- α (IFN-1)或白细胞介素-2 （IL2）的广泛细胞因子刺激是转移性RCC的有效治疗方法。最近对疾病机制的了解取得了进展，这使得开发出更具体的治疗方法成为可能。透明细胞RCC以von Hippel Lindau （VHL）基因突变为特征，导致下游基因产物如血管内皮生长因子（VEGF）过表达。贝伐单抗是一种单克隆抗体，结合并中和VEGF蛋白的所有亚型，目前正在晚期RCC的临床试验中进行研究。CALGB 90206随机化未经治疗的转移性透明细胞RCC患者单独使用IFN-1或IFN-1联合贝伐单抗。在达到700多名患者的目标后，该研究现已关闭入组。作为研究的一部分，预处理石蜡RCC肿瘤块被储存起来进行相关研究。这个与临床结果相关的肿瘤组织储存库为推进基因表达科学作为预测和预后工具提供了宝贵的资源。我们建议使用一种定量的、基于逆转录PCR的方法来评估相关基因的mRNA水平。基因表达水平用于建立预测治疗反应的模型，确定预后，并评估与RCC相关的分子缺陷的可变性。该分析的见解将对实体肿瘤和多种抗血管生成模式具有广泛的意义。肾癌的治疗包括免疫调节和抑制新血管的形成。本研究使用CALGB 90206收集的肿瘤组织，CALGB 90206是一项晚期肾癌临床试验，评估免疫治疗是否抑制血管形成，以确定可以预测生存和治疗反应的分子标记。公共卫生相关性：肾癌的治疗包括免疫调节和抑制新血管的形成。本研究使用CALGB 90206收集的肿瘤组织，CALGB 90206是一项晚期肾癌临床试验，评估免疫治疗是否抑制血管形成，以确定可以预测生存和治疗反应的分子标记。