Salinomycin, a polyether antibiotic, inhibited PTEN-null castration-sensitive and castration-resistant prostate cancer cells for expansion in vitro and in tumor xenografts, and prevented a compensatory negative crosstalk between AR and mTORC1, which otherwise would have led to reciprocal activation of the two oncogenic pathways, causing activation of one when the other is blocked. The gene discussed is AR; the disease is prostate carcinoma.