CDKN1A and hereditary clear cell renal cell carcinoma: For instance, DAB2IP modulates resistance to mTOR inhibitors in advanced renal cell carcinoma; reduced DAB2IP expression caused by epigenetic silencing by EZH2 results in hyper-activation of extracellular signal-regulated kinase/RSK1 and the PI3K/mTOR pathway, which induces the expression of HIF-2α and the consequent inhibition of p21/WAF1 expression, associated with resistance to mTOR inhibitors [33, 34].