Thus, although the clinical relevance of the RAS-mediated resistance against ErbB2 blockade still needs to be proven, promising results from phase I studies of the RAS FT inhibitor lonafarnib, administered in combination with trastuzumab plus paclitaxel—showing a respectable objective response rate of 58% in treatment of advanced ErbB2-overexpressing breast cancer—or regimens combining AKT inhibitor MK2206 with trastuzumab, underscore the potential of therapeutic intervention at the RAS-PI3K-AKT axis in the treatment of ErbB2-addicted breast cancers52, 53. Here, PIK3CA is linked to breast carcinoma.