Sorafenib, a tyrosine kinase inhibitor, was effective in reducing p21 levels in renal and hepatocellular carcinoma cells, and its combination with other cytotoxic drugs shows additive effects, suggesting that sorafenib may act as a sensitizing agent for chemotherapeutics used to treat renal cell carcinoma (RCC) by modulating p21 levels. Here, CDKN1A is linked to hereditary clear cell renal cell carcinoma.