Our finding that the group II PAK inhibitor GNE-2861, which does not inhibit group I PAKs (PAK1, 2, 3) [31], restored tamoxifen sensitivity, in combination with the induction of tamoxifen resistance by PAK4 overexpression and the correlation of high PAK4 expression with poor patient outcome after tamoxifen treatment now suggest that PAK4 may promote tamoxifen resistance in ERα positive breast cancer. This evidence concerns the gene ESR1 and breast carcinoma.