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In the tumor microenvironment, this likely helps them evade therapies that target specific pathways. We must identify all possible states and utilize them in drug screening programs. One such state is characterized by expression of the transcription factor Hairy and Enhancer of Split 3 (\n                    <jats:italic>HES3<\/jats:italic>\n                    ) and sensitivity to\n                    <jats:italic>HES3<\/jats:italic>\n                    knockdown, and it can be modeled\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Here, we cultured 3 primary human brain cancer cell lines under 3 different culture conditions that maintain low, medium, and high\n                    <jats:italic>HES3<\/jats:italic>\n                    expression and characterized gene regulation and mechanical phenotype in these states. We assessed gene expression regulation following\n                    <jats:italic>HES3<\/jats:italic>\n                    knockdown in the\n                    <jats:italic>HES3<\/jats:italic>\n                    \u2010high conditions. We then employed a commonly used human brain tumor cell line to screen Food and Drug Administration (FDA)\u2010approved compounds that specifically target the\n                    <jats:italic>HES3<\/jats:italic>\n                    \u2010high state. We report that cells from multiple patients behave similarly when placed under distinct culture conditions. We identified 37 FDA\u2010approved compounds that specifically kill cancer cells in the high\u2010\n                    <jats:italic>HES3<\/jats:italic>\n                    \u2013expression conditions. Our work reveals a novel signaling state in cancer, biomarkers, a strategy to identify treatments against it, and a set of putative drugs for potential repurposing.\u2014Poser, S. W., Otto, O., Arps\u2010Forker, C., Ge, Y., Herbig, M., Andree, C., Gruetzmann, K., Adasme, M. F., Stodolak, S., Nikolakopoulou, P., Park, D. M., Mcintyre, A., Lesche, M., Dahl, A., Lennig, P., Bornstein, S. R., Schroeck, E., Klink, B., Leker, R. R., Bickle, M., Chrousos, G. P., Schroeder, M., Cannistraci, C. V., Guck, J., Androutsellis\u2010Theotokis, A. Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery. FASEB J. 33, 9235\u20139249 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802603rr","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T14:00:36Z","timestamp":1559224836000},"page":"9235-9249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery"],"prefix":"10.1096","volume":"33","author":[{"given":"Steven W.","family":"Poser","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Otto","sequence":"additional","affiliation":[{"name":"Biotechnology Center 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