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Metastatic non-clear cell renal cell carcinoma: an evidence based review of current treatment strategies.

ABSTRACT: Much progress has been made in the treatment of metastatic renal cell carcinoma (RCC) over the last decade, with the development of agents that block the vascular endothelial growth factor (VEGF) pathway or the mammalian target of rapamycin (mTOR) pathway. The incorporation of these agents into treatment algorithms has been the result of carefully conducted clinical trials leading to Food and Drug Administration (FDA) approval and subsequent adoption as the current standard of care. These trials, however, were dominated by patients with clear cell renal cell carcinoma (ccRCC), and little data are currently available on the treatment of non-clear cell renal cell carcinoma (nccRCC). nccRCC encompasses a biologically heterogeneous group of kidney tumors that portend very diverse prognoses and responses to therapy. This review is a pathway based approach that highlights the current systemic treatment strategies for metastatic nccRCC.

SUBMITTER: Sankin A

PROVIDER: S-EPMC4389537 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Metastatic non-clear cell renal cell carcinoma: an evidence based review of current treatment strategies.

Sankin Alexander A Hakimi A Ari AA Hsieh James J JJ Molina Ana M AM

Frontiers in oncology 20150408

Much progress has been made in the treatment of metastatic renal cell carcinoma (RCC) over the last decade, with the development of agents that block the vascular endothelial growth factor (VEGF) pathway or the mammalian target of rapamycin (mTOR) pathway. The incorporation of these agents into treatment algorithms has been the result of carefully conducted clinical trials leading to Food and Drug Administration (FDA) approval and subsequent adoption as the current standard of care. These trials ...[more]

PMID: 25905038

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Project description:BACKGROUND:Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress. METHOD:Diagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters. RESULTS:The ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p?<?0.001), TNM stage (p?<?0.001), morphological grade (p?<?0.001), and patients outcome (5?year cancer specific survival (pCSS5yr) p?<?0.001 and cumulative incidence of progress (pCIP5yr) p?<?0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R?=?0.435, p?<?0.001), and predicted mitotic age (R?=?0.407, p?<?0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p?=?0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p?<?0.001). CONCLUSION:DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.

Dataset Information

Metastatic non-clear cell renal cell carcinoma: an evidence based review of current treatment strategies.

Publications

Metastatic non-clear cell renal cell carcinoma: an evidence based review of current treatment strategies.

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