Sertraline inhibited cell proliferation in MCF‐7 cells via inhibition of translation initiation, downregulation of eIF4F complex and increased eIF2α phosphorylation and REDD1 expression, leading to suppression of mTOR signalingSertraline sensitized Pten+/−Eμ‐Myc tumors to doxorubicin, increasing tumor‐free survival compared to monotherapyNo synergistic effect was seen in Eμ‐Myc/Bcl‐2 or Eμ‐Myc/eIF4E tumors, suggesting the response is genotype‐dependentIn vivo, sertraline treatment reduced protein synthesis, as shown by polysome profile analysis in tumors. Here, DDIT4 is linked to neoplasm.