NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy

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The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion.

A recent exome sequencing study identified truncating mutations of PBRM1 in 92 of 227 (41%) cases of clear cell RCC. PBRM1 codes for BAF180 protein, a subunit of the PBAF SWI/SNF chromatin remodeling complex, and is implicated in replication, transcription, and control of cell proliferation and differentiation. This gene, like VHL and SETD2, is located on chromosome 3p21. (Reference: Varela I, Tarpey P, Raine K, et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 2011;469:539–542.)

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