KDR and cancer: Finally, the RAS activation signature is observed in approximately 25% of KRAS wild-type cancers [53] because increased RAS activity in human cancers can result from RAS gene amplification [184, 185] or overexpression [55], an increase in upstream signals from tyrosine kinase growth factor receptors such as HER2 and EGFR [56, 57], or a decrease in the expression of microRNAs such as let-7 family members [58].