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：
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
项目类别：
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

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）：新诊断的肾细胞癌（RCC）患者中有三分之一患有转移性疾病。在最初诊断为局限性肾细胞癌的患者中，尽管对原发肿瘤进行了治疗，但仍有三分之一最终会出现转移性疾病。 RCC 对传统化疗和放疗具有抵抗力，使用干扰素 α (IFN-1) 或白细胞介素 2 (IL2) 进行全身细胞因子刺激是转移性 RCC 的有效治疗方法。最近对该疾病机制的了解取得了进展，使得更具体的治疗方法得以开发。透明细胞肾细胞癌的特点是 von Hippel Lindau (VHL) 基因突变，导致血管内皮生长因子 (VEGF) 等下游基因产物过度表达。贝伐珠单抗是一种单克隆抗体，可结合并中和 VEGF 蛋白的所有亚型，目前正在晚期肾细胞癌的临床试验中进行研究。 CALGB 90206 将未经治疗的转移性透明细胞 RCC 患者随机分配至单独使用 IFN-1 或使用 IFN-1 加贝伐单抗。在达到 700 多名患者的目标后，该研究现已结束招募。作为研究的一部分，治疗前的石蜡 RCC 肿瘤块被储存起来用于相关研究。这个具有相关临床结果的大型肿瘤组织库代表了推进基因表达科学作为预测和预后工具的宝贵资源。我们建议使用基于逆转录 PCR 的定量方法来评估相关基因的 mRNA 水平。基因表达水平用于开发模型来预测治疗反应、确定预后以及评估与 RCC 相关的分子缺陷的变异性。该分析的见解将对实体瘤和多种抗血管生成方式产生广泛影响。肾癌的治疗包括免疫调节和抑制新血管形成。这项研究使用作为 CALGB 90206 的一部分收集的肿瘤组织，这是一项针对晚期肾癌的临床试验，评估有或没有抑制血管形成的免疫疗法，以确定可以预测生存和治疗反应的分子标记。公众健康相关性：肾癌的治疗包括免疫调节和抑制新血管形成。这项研究使用作为 CALGB 90206 的一部分收集的肿瘤组织，这是一项针对晚期肾癌的临床试验，评估有或没有抑制血管形成的免疫疗法，以确定可以预测生存和治疗反应的分子标记。