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RNA polymerases trapped in DNA can be a source of transcription-replication conflict (T-R conflict), which is a common source of replication stress.\u00a0AZD4573, a highly selective CDK9 inhibitor, has been shown to induce apoptosis in leukemia\u00a0cell lines, while its anti-tumor potential in breast cancer has yet to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To evaluate the cytotoxicity of AZD4573 in vitro, MTT assays were performed. The expression of signal transduction molecules was determined using Western blotting, immunoprecipitation, and immunofluorescence. Apoptotic cell death was verified by the annexin-V assay. DNA strand breaks and repair efficacy were evaluated through the alkaline comet assay. The siRNA knock-down system was used to confirm the action mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AZD4573 induced T-R conflicts during S-phase, increasing replication stress and DNA strand breaks, resulting in apoptosis by induction of caspase-3. Furthermore, we identified Dead-box 25 (DDX25) helicase as a key mediator in resolving the T-R conflicts. Nuclear translocation of DDX25 correlated with reduced sensitivity to AZD4573 by the resolution of T-R conflicts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibition of CDK9 by AZD4573 induces the accumulation of DNA damage through T-R conflicts. DDX25 helicases were identified as a key mediator in resolving T-R conflicts and the reduced sensitivity to AZD4573.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12935-025-03897-6","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T14:26:53Z","timestamp":1753453613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cyclin dependent kinase 9 inhibitor induces transcription-replication conflicts and DNA damage accumulation in breast cancer"],"prefix":"10.1186","volume":"25","author":[{"given":"Minyoung","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Hun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahrum","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Hyeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujin","family":"Ham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Min","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youlim","family":"Noh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Won","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwon","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seock-Ah","family":"Im","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"issue":"3","key":"3897_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. 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The maximal volume of tumor was permitted by their ethics committee was 2000 mm\n                      3\n                      . All the tumor in this study were below 2000 mm\n                      3\n                      .","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Seock-Ah Im is a recipient of research funds from AstraZeneca Inc., Boryung Pharm, Daiichi Sankyo Co., Ltd, Daewoong Pharm, Pfizer, Roche and has consultant and advisory role for AstraZeneca, Daiichi Sankyo, Eisai, Hanmi Corp, MSD, Novartis, Pfizer, and Roche. Kyung-Hun Lee reports honoraria from AstraZeneca, Boryung Pharm, Daiichi Sankyo, Eli Lilly, Novartis, and Pfizer. Jiwon Koh has advisory role for AstraZeneca outside of this work. The other authors declared that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"282"}}