{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:22:14Z","timestamp":1790835734138,"version":"4.1.0"},"reference-count":84,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tumor Biology Training","award":["T32 CA009686"],"award-info":[{"award-number":["T32 CA009686"]}]},{"name":"Georgetown Undergraduate Research Opportunities Program"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Resistance to endocrine therapy in estrogen receptor\u2013positive (ER+) breast cancer remains a significant clinical problem. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis. A benzothiazole-based glutamate release inhibitor with several context-dependent mechanism(s) of action, riluzole has shown antitumor activity in multiple malignancies, including melanoma, glioblastoma, and breast cancer. We previously reported that the acquisition of tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by riluzole.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We tested the ability of riluzole to reduce cell growth, alone and in combination with endocrine therapy, in a diverse set of ER+ invasive ductal and lobular breast cancer\u2013derived cell lines, primary breast tumor explant cultures, and the estrogen-independent, ESR1-mutated invasive lobular breast cancer patient-derived xenograft model HCI-013EI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Single-agent riluzole suppressed the growth of ER+ invasive ductal and lobular breast cancer cell lines in vitro, inducing a histologic subtype-associated cell cycle arrest (G0-G1 for ductal, G2-M for lobular). Riluzole induced apoptosis and ferroptosis and reduced phosphorylation of multiple prosurvival signaling molecules, including Akt\/mTOR, CREB, and Fak\/Src family kinases. Riluzole, in combination with either fulvestrant or 4-hydroxytamoxifen, additively suppressed ER+ breast cancer cell growth in vitro. Single-agent riluzole significantly inhibited HCI-013EI patient-derived xenograft growth in vivo, and the combination of riluzole plus fulvestrant significantly reduced proliferation in ex vivo primary breast tumor explant cultures.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvad117","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T17:10:54Z","timestamp":1694797854000},"source":"Crossref","is-referenced-by-count":11,"title":["Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer"],"prefix":"10.1210","volume":"7","author":[{"given":"Ayodeji O","family":"Olukoya","sequence":"first","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-2024","authenticated-orcid":false,"given":"Hillary","family":"Stires","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9882-4195","authenticated-orcid":false,"given":"Shaymaa","family":"Bahnassy","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Persaud","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanira","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3058-6332","authenticated-orcid":false,"given":"Suman","family":"Ranjit","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihong","family":"Ma","sequence":"additional","affiliation":[{"name":"Departments of Urology and Pharmacology, University of Texas Southwestern Medical Center at Dallas , Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Idalia","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Benitez","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M","family":"Rozeboom","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0477-150X","authenticated-orcid":false,"given":"Hannah","family":"Ceuleers","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, DC 20057 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-1690","authenticated-orcid":false,"given":"Britta M","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Anschutz Medical Campus , Denver, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5098-6347","authenticated-orcid":false,"given":"Ganesh V","family":"Raj","sequence":"additional","affiliation":[{"name":"Departments of Urology and Pharmacology, University of Texas Southwestern Medical Center at Dallas , Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1555-4431","authenticated-orcid":false,"given":"Rebecca 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