Expression profiling of renal cell carcinoma utilizing tissue from CALGB 90206

描述(申请人提供)：在新诊断的肾细胞癌患者中，有三分之一有转移性疾病。在最初诊断为局限性肾细胞癌的患者中，有三分之一最终会发展为转移性疾病，尽管对原发肿瘤进行了治疗。肾癌对常规化疗和放疗耐药，干扰素-1或白介素2(IL-2)联合全身细胞因子刺激是治疗转移性肾癌的有效方法。最近在了解疾病机制方面的进展使更具体的治疗方法得以开发。透明细胞肾癌的特征是von Hippel Lindau(VHL)基因突变，导致下游基因产物如血管内皮生长因子(VEGF)的过度表达。贝伐单抗是一种能结合和中和所有异构体的血管内皮生长因子蛋白的单抗，目前正在进行晚期肾癌的临床试验。CALGB 90206将未经治疗的转移性透明细胞肾癌患者随机分为干扰素-1组或干扰素-1+贝伐单抗组。这项研究在达到了700多名患者的目标收益后，现在已经接近登记。作为研究的一部分，对治疗前的石蜡肾细胞癌肿瘤块进行了相关研究。这一庞大的肿瘤组织库与临床结果相关联，为推动基因表达科学作为预测和预后工具提供了宝贵的资源。我们建议使用基于逆转录聚合酶链式反应的定量方法来评估相关基因的信使核糖核酸水平。基因表达水平被用来开发预测治疗反应、确定预后和评估与肾癌相关的分子缺陷的变异性的模型。这项分析的见解将对实体肿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。这项研究使用收集的肿瘤组织作为CALGB 90206的一部分，CALGB 100是一项晚期肾癌的临床试验，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。这项研究使用收集的肿瘤组织作为CALGB 90206的一部分，CALGB 100是一项晚期肾癌的临床试验，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.