The role of mTOR documented here for E2 stimulation of PTHrP secretion in bone tropic ER+ cells forming osteolytic lesions in vivo is specifically of clinical relevance as recent clinical trials evaluating the efficacy of combining hormone therapy with mTOR inhibitors (such as everolimus) have proven effective in patients with advanced ER+ breast cancer (including those with BMETs), with results reported here possibility providing additional mechanistic insights [66]. The gene discussed is ESR1; the disease is breast carcinoma.