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. The gene discussed is PAK4; the disease is breast carcinoma.