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

肾细胞癌（RCC）历来被认为是一个单一的实体，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了生存率。但到目前为止，对于不常见但更具侵袭性的2型乳头状肾细胞癌，还没有标准的治疗方法，对这种疾病的潜在分子特征也知之甚少。该研究的目的是确定2型乳头状肾细胞癌的基因组特征。研究结果将与患者的临床结果相关联，以确定疾病进展和药物反应的基因组预测因子。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标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）的多机构池中招募。已建立的对患者原发肿瘤和转移组织的多路并行深度测序方法将在MSKCC的跨实验室合作中进行。结果将通过回归分析与患者的临床病程相关联。将创建细胞系和异种移植物来分析药物反应。该项目将确定疾病进展的预测因子，并将确定“可药物”基因，用于未来靶向治疗的开发。此外，人鼠模型将潜在地帮助临床医生使用当前可用的药物提供量身定制的治疗方案。

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.