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

• Applicant: Dr. Jozefina Casuscelli
• Subject Area: Reproductive Medicine, Urology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261474603

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.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. James Hsieh