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Recent studies have shown that the mTORC1 inhibitor rapamycin and its analogs generally suppress proliferation rather than induce apoptosis. Therefore, it is critical to use alternative strategies to induce death of cells with activated mTORC1. In this study, a small-molecule screen has revealed that the combination of glutaminase (GLS) and heat shock protein 90 (Hsp90) inhibitors selectively triggers death of\n                    <jats:italic>TSC2<\/jats:italic>\n                    -deficient cells. At a mechanistic level, high mTORC1-driven translation rates in\n                    <jats:italic>TSC1\/2<\/jats:italic>\n                    -deficient cells, unlike wild-type cells, sensitizes these cells to endoplasmic reticulum (ER) stress. Thus, Hsp90 inhibition drives accumulation of unfolded protein and ER stress. When combining proteotoxic stress with oxidative stress by depletion of the intracellular antioxidant glutathione by GLS inhibition, acute cell death is observed in cells with activated mTORC1 signaling. This study suggests that this combination strategy may have the potential to be developed into a therapeutic use for the treatment of mTORC1-driven tumors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1417015112","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T06:20:03Z","timestamp":1418970003000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":42,"title":["RETRACTED: Synthetic lethality of combined glutaminase and Hsp90 inhibition in mTORC1-driven tumor cells"],"prefix":"10.1073","volume":"112","author":[{"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Csibi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 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