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Ovarian cancer (OvCa) cells persist in poorly vascularized scars on the peritoneal surface and depend on autophagy to survive nutrient deprivation. The authors have sought drugs that target autophagic cancer cells selectively to eliminate residual disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By using unbiased small\u2010interfering RNA (siRNA) screens, the authors observed that knockdown of anaplastic lymphoma kinase (ALK) reduced the survival of autophagic OvCa cells. Small\u2010molecule ALK inhibitors were evaluated for their selective toxicity against autophagic OvCa cell lines and xenografts. Autophagy was induced by reexpression of GTP\u2010binding protein Di\u2010Ras3 (DIRAS3) or serum starvation and was evaluated with Western blot analysis, fluorescence imaging, and transmission electron microscopy. Signaling pathways required for crizotinib\u2010induced apoptosis of autophagic cells were explored with flow cytometric analysis, Western blot analysis, short\u2010hairpin RNA knockdown of autophagic proteins, and small\u2010molecule inhibitors of STAT3 and BCL\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Induction of autophagy by reexpression of DIRAS3 or serum starvation in multiple OvCa cell lines significantly reduced the 50% inhibitory concentration of crizotinib and other ALK inhibitors. In 2 human OvCa xenograft models, the DIRAS3\u2010expressing tumors treated with crizotinib had significantly decreased tumor burden and long\u2010term survival in 67% to 79% of mice. Crizotinib treatment of autophagic cancer cells further enhanced autophagy and induced autophagy\u2010mediated apoptosis by decreasing phosphorylated STAT3 and BCL\u20102 signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Crizotinib may eliminate dormant, autophagic, drug\u2010resistant OvCa cells that remain after conventional cytoreductive surgery and combination chemotherapy. A clinical trial of ALK inhibitors as maintenance therapy after second\u2010look operations should be seriously considered.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.32985","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T14:34:56Z","timestamp":1591108496000},"page":"3579-3592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Elimination of dormant, autophagic ovarian cancer cells and xenografts through enhanced sensitivity to anaplastic lymphoma kinase inhibition"],"prefix":"10.1002","volume":"126","author":[{"given":"Alicia M.","family":"Blessing","sequence":"first","affiliation":[{"name":"Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice M.","family":"Santiago\u2010O'Farrill","sequence":"additional","affiliation":[{"name":"Department of 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