VHL and nonpapillary renal cell carcinoma: While ccRCC is not commonly associated with DDR deficiency, recent in-vitro and in-vivo data demonstrating replication stress as a consequence of common mutations associated with RCC (VHL loss: 85% of ccRCC, SETD2 mutations: 12% of ccRCC) and VEGF inhibition suggest that DDR-targeted treatment may be an effective and relevant therapeutic strategy [20, 21].