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

基本信息

批准号：
7851081
负责人：
HYUNG L KIM
金额：
$ 42.99万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7851081
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 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 public health relevance randomized trial repository response tool treatment response tumor tumorigenesis

项目摘要

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）的患者患有转移性疾病。在最初被诊断为局部RCC的患者中，尽管治疗了原发性肿瘤，但最终将最终患上转移性疾病。 RCC对常规化学疗法和辐射具有抗性，并且对干扰素-α（IFN-1）或白介素-2（IL2）的广义细胞因子刺激代表了转移性RCC的有效治疗方法。了解疾病机制的最新进展允许发展更具体的治疗方法。透明细胞RCC的特征是von Hippel -Lindau（VHL）基因突变，这导致下游基因产物（例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，可结合并中和VEGF蛋白的所有同工型，并在晚期RCC的临床试验中进行了研究。 CALGB 90206单独使用IFN-1或IFN-1加贝伐单抗的随机未经治疗的转移性清除细胞RCC患者。该研究现已在达到700多名患者的目标应计后入学率关闭。作为研究的一部分，对治疗前的石蜡RCC肿瘤块进行了研究，以进行相关研究。这个具有连接临床结果的肿瘤组织的大仓库代表了推进基因表达科学作为一种预测性和预后工具的宝贵资源。我们建议使用基于定量的，逆转录PCR的方法评估相关基因的mRNA水平。基因表达水平用于开发模型，以预测对治疗的反应，确定预后以及评估与RCC相关的分子缺陷的变异性。该分析的见解将在实体瘤和多种抗血管生成方式之间具有广泛的影响。肾癌的治疗包括免疫调节和抑制新血管形成。这项研究使用收集的肿瘤组织作为CALGB 90206的一部分，这是一项用于评估免疫疗法的晚期肾癌试验，无论有或不抑制血管形成，以鉴定可以预测可以预测治疗生存和反应的分子标记。公共卫生相关性：肾癌的治疗方法包括免疫调节和抑制新血管形成。这项研究使用收集的肿瘤组织作为CALGB 90206的一部分，这是一项用于评估免疫疗法的晚期肾癌试验，无论有或不抑制血管形成，以鉴定可以预测可以预测治疗生存和反应的分子标记。