Subsequent validation in HCC models via MEK/ERK phosphorylation blockade expanded therapeutic validation into the #11 sorafenib cluster (Liu et al., 2006), while the SHARP trial extended this paradigm to pan-cancer VEGF/PDGF inhibition through the #18 advanced clear-cell renal-cell carcinoma cluster (Llovet et al., 2008; Cheng et al., 2009; Ebos et al., 2009). This evidence concerns the gene MAP2K7 and clear cell renal carcinoma.