Gene activity and gene silencing tests in clear cell kidney cancer identify PLK1 and other protein kinases as treatment targets

Gene expression profiling of 90 ccRCC patient specimens identified Polo-like kinase 1 (PLK1) as a potential therapeutic target.

• Gene set enrichment analysis found that cell-cycle-related genes are linked to disease aggressiveness in ccRCC.
• Inhibition of PLK1 and other cell-cycle kinases reduced cell proliferation in ccRCC cell cultures.
• A small-molecule inhibitor of PLK1, BI 2536, effectively inhibited ccRCC cell line proliferation at appropriate concentrations.
• Sustained PLK1 inhibition by BI 2536 resulted in significant regression of ccRCC xenograft tumors in animal models.

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