{"doi":"10.1210/jendso/bvad117","title":"Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer","abstract":"Background: Resistance to endocrine therapy in estrogen receptor-positive (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. Methods: -mutated invasive lobular breast cancer patient-derived xenograft model HCI-013EI. Results: 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. Conclusion: Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.","journal":"Journal of the Endocrine Society","year":2023,"id":358711,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":565511,"name":"Hillary Stires","orcid":null,"position":1,"is_corresponding":false},{"id":564879,"name":"Shaymaa Bahnassy","orcid":"0000-0001-9882-4195","position":2,"is_corresponding":false},{"id":565512,"name":"Sonali Persaud","orcid":null,"position":3,"is_corresponding":false},{"id":565513,"name":"Yanira Guerra","orcid":null,"position":4,"is_corresponding":false},{"id":288785,"name":"Suman Ranjit","orcid":"0000-0003-3058-6332","position":5,"is_corresponding":false},{"id":385821,"name":"Shihong Ma","orcid":"0000-0001-5903-2785","position":6,"is_corresponding":false},{"id":405450,"name":"M. Idalia Cruz","orcid":"0009-0006-5530-2876","position":7,"is_corresponding":false},{"id":565514,"name":"Carlos Benitez","orcid":null,"position":8,"is_corresponding":false},{"id":565515,"name":"Aaron M. Rozeboom","orcid":null,"position":9,"is_corresponding":false},{"id":564880,"name":"Hannah Ceuleers","orcid":"0000-0003-0477-150X","position":10,"is_corresponding":false},{"id":406109,"name":"Deborah L. Berry","orcid":null,"position":11,"is_corresponding":false},{"id":319602,"name":"Britta M. Jacobsen","orcid":"0000-0001-8234-1690","position":12,"is_corresponding":false},{"id":318298,"name":"Ganesh V. Raj","orcid":"0000-0001-5098-6347","position":13,"is_corresponding":false},{"id":319601,"name":"Rebecca B. Riggins","orcid":"0000-0002-1555-4431","position":14,"is_corresponding":false},{"id":565510,"name":"Ayodeji Olukoya","orcid":null,"position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T01:13:48.379546Z","pmid":"37766843","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}