{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:45:48Z","timestamp":1792082748810,"version":"4.4.0"},"reference-count":53,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health (NIH)"},{"name":"Elsa Pardee Foundation"},{"name":"Lubin Family Foundation Fellowship Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ewing sarcoma is an aggressive pediatric cancer for which no targeted therapies have been approved. This disease is driven by EWSR1::ETS family fusions that, like most fusion transcription factors, have proven difficult to target directly. Here, we focus on identifying actionable dependencies within the high-risk STAG2-mutant (STAG2-mut) disease subtype of Ewing sarcoma. In STAG2-mut Ewing sarcoma, STAG1 knockout is synthetically lethal but is not readily druggable. Using the Cancer Dependency Map (DepMap), we identify histone deacetylase 8 (HDAC8) as an enriched vulnerability in this molecular context. CRISPR validation and a newly developed HDAC8 degrader, XY-09-36, confirm this selective dependency and suggest increased reliance on HDAC8-mediated cohesin regulation when STAG2 is lost. These findings establish HDAC8 as a context-dependent, pharmacologically accessible vulnerability and outline a framework for discovering rational targets in tumor subtypes where primary drivers are intrinsically hard to drug.<\/jats:p>","DOI":"10.1021\/acschembio.6c00345","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:00:21Z","timestamp":1788253221000},"page":"2188-2199","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of HDAC8 as a Druggable Target in\n                    <i>STAG2<\/i>\n                    -Mutant Ewing Sarcoma"],"prefix":"10.1021","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0129-2773","authenticated-orcid":true,"given":"Olasunkanmi","family":"Olaoye","sequence":"first","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2211-8267","authenticated-orcid":true,"given":"Yuan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , ,","place":["Boston, MA, USA, 02215"]},{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory D.","family":"Rillahan","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biniam","family":"Adane","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"DiGiovanni","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth N.","family":"Ross","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Alexe","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Howard","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Kirmani","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , ,","place":["Boston, MA, USA, 02215"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0605-0071","authenticated-orcid":true,"given":"Rados\u0142aw P.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , ,","place":["Boston, MA, USA, 02215"]},{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Donovan","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , ,","place":["Boston, MA, USA, 02215"]},{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7337-6306","authenticated-orcid":true,"given":"Eric S.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , ,","place":["Boston, MA, USA, 02215"]},{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Stegmaier","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, MA, USA, 02215"]},{"name":"Broad Institute of MIT and Harvard , , ,","place":["Cambridge, MA, USA, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"6432","key":"2026101511063518300_cit1","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1126\/science.aaw3535","article-title":"The Genomic Landscape of Pediatric Cancers: Implications for Diagnosis and Treatment","volume":"363","author":"Alejandro Sweet-Cordero","year":"2019","journal-title":"Science"},{"key":"2026101511063518300_cit2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.omtn.2017.01.005","article-title":"Relevance of Fusion Genes in Pediatric Cancers: Toward Precision Medicine","volume":"6","author":"Dupain","year":"2017","journal-title":"Mol. 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