Papillary type 2 renal cell carcinoma: Characterization and observation of genetic changes during therapy with target agents and correlation to real patient's clinical course

2 型乳头状肾细胞癌：靶向药物治疗过程中基因变化的表征和观察以及与真实患者临床病程的相关性

• 批准号: 261474603
• 负责人: Dr. Jozefina Casuscelli
• 金额: --
• 依托单位: Human Oncology and Pathogenesis Program
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/261474603?language=en
• 关键词: Papillary; type; renal; cell; carcinoma

Renal cell carcinoma (RCC) has historically been viewed as a single entity, but distinct subtypes have been identified in past decades. For the most common subtype, clear cell RCC, new targeted drugs significantly improved survival. But to date, no standard of care exists for the less common but more aggressive papillary type 2 RCC and little is known about the underlying molecular characteristics of this disease. The aim of the study is to identify the genomic characteristics of papillary type 2 RCC. Findings will be correlated to clinical outcomes of patients to define genomic predictors of disease progression and drug response. In addition, generation of real-time kidney cancer xenografts will enable direct monitoring of response and resistance development to current target drugs. The studies will be based on the globally largest cohort of patients, recruited from both, the Ludwig-Maximilians-University in Munich and a multi-institutional pool from Memorial Sloan Kettering Cancer Center (MSKCC). Established methods of multiplexed massively parallel deep sequencing on patient's primary tumor and metastatic tissue will be performed in cross-lab collaboration at MSKCC. Findings will be correlated to patient's clinical course via regression analysis. Cell lines and xenografts will be created to analyze drug response. This project will define predictors of disease progression and will determine "druggable" genes for the development of future targeted therapeutics. Furthermore the human-in-mouse models will potentially assist clinicians to provide tailored treatment options with the current available drugs.

肾细胞癌（RCC）历来被视为一个单一的实体，但在过去的几十年中已经确定了不同的亚型。对于最常见的亚型，透明细胞RCC，新的靶向药物显着提高生存率。但到目前为止，对于不太常见但更具侵袭性的乳头状2型RCC没有标准的治疗方法，并且对这种疾病的潜在分子特征知之甚少。本研究的目的是确定乳头状2型肾细胞癌的基因组特征。研究结果将与患者的临床结局相关，以确定疾病进展和药物应答的基因组预测因子。此外，实时肾癌异种移植物的产生将能够直接监测对当前靶向药物的反应和耐药性发展。这些研究将基于全球最大的患者队列，从慕尼黑的路德维希-马克西米利安大学和纪念斯隆-凯特琳癌症中心（MSKCC）的多机构库招募。将在MSKCC的跨实验室合作中对患者的原发性肿瘤和转移性组织进行多重大规模平行深度测序。通过回归分析将结果与患者的临床病程相关联。将创建细胞系和异种移植物以分析药物反应。该项目将定义疾病进展的预测因子，并确定未来靶向治疗药物开发的“可药物化”基因。此外，人在小鼠模型将有可能帮助临床医生提供定制的治疗方案与目前可用的药物。