Expression profiling of renal cell carcinoma utilizing tissue from CALGB 90206

描述（由申请人提供）：三分之一新诊断为肾细胞癌（RCC）的患者患有转移性疾病。在最初诊断为局部RCC的患者中，三分之一的患者尽管接受了原发性肿瘤的治疗，但最终仍会发生转移性疾病。RCC对常规化疗和放疗具有抗性，并且用干扰素-α（IFN-1）或白细胞介素-2（IL-2）的广义细胞因子刺激代表了转移性RCC的有效治疗。对疾病机制的理解的最新进展允许开发更具体的治疗方法。透明细胞肾细胞癌的特征在于von Hippel Lindau（VHL）基因突变，其导致下游基因产物如血管内皮生长因子（VEGF）的过度表达。贝伐单抗是一种单克隆抗体，可结合并中和VEGF蛋白的所有亚型，目前正在晚期RCC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的IFN-1或IFN-1加贝伐单抗。该研究在达到700多名患者的目标入组后，现已关闭入组。作为研究的一部分，将治疗前石蜡RCC肿瘤块储存用于相关研究。这种具有相关临床结果的肿瘤组织的大型储存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。我们建议使用定量，逆转录PCR为基础的方法来评估相关基因的mRNA水平。基因表达水平被用来开发模型，用于预测对治疗的反应，确定预后，并评估与RCC相关的分子缺陷的变异性。这项分析的见解将对实体瘤和多种抗血管生成方式产生广泛的影响。肾癌的治疗包括免疫调节和抑制新血管形成。这项研究使用了作为CALGB 90206的一部分收集的肿瘤组织，CALGB 90206是一项评估有或没有抑制血管形成的免疫治疗的晚期肾癌临床试验，以确定可以预测生存和治疗反应的分子标志物。公共卫生相关性：肾癌的治疗包括免疫调节和抑制新血管形成。这项研究使用了作为CALGB 90206的一部分收集的肿瘤组织，CALGB 90206是一项评估有或没有抑制血管形成的免疫治疗的晚期肾癌临床试验，以确定可以预测生存和治疗反应的分子标志物。

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.