https://m2.mtmt.hu/ hun 2026-05-31 11:18 JournalArticle 34867519 VALIDATED true Funding Agency and Grant Number: E.I. Stiftung Koelner Krebsforschung; Jurgen Manchot Stiftung; Deutsche Forschungsgemeinschaft (DFG) [455784452, ID:01ZX1901, 70115679, 1117240, 01ZX1303A, 2020-090, NLP-17, 2022-2.1.1-NL-2022-00010]; The NRW Network consortium CANTAR [TKP2021-EGA-44]; German Ministry of Science and Education (BMBF); National Laboratories Excellence program [under the National Tumour Biology Laboratory Project] [2016_Kolleg.19, 70113041]; Hungarian Thematic Excellence Programme [70113307]; Else Kroener-Fresenius Stiftung [01KU2104, Ex-2021-0033]; Deutsche Krebshilfe [214342/Z/18/Z]; Mildred Scheel Nachwuchszentrum Grant [294880]; Ministerio de Ciencia e Innovacion, Proyectos I + D + i Pruebas de Concepto; German Ministry of Education and Research (BMBF); Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya; Consortium HiRisk-HiGain ERAPERMED [A27323]; MERCUR Foundation [MR/S00811X/1]; Wellcome Trust [RTI2018-094533-A-I00]; ERC Advanced Grant [PID2021-128644OB-I0]; Cancer Research UK programme grant [PDC2022-133583-I00]; MRC [2021-SGR-00284]; Alexander von Humboldt Professorship Award; Mildred Scheel School of Oncology [294880]; Ministerio de Ciencia, Innovacion y Universidades [SFB1403]; Ministerio de Ciencia e Innovacion, Proy. de Generacion del Conocimiento [414786233]; [RE 2246/13-1]; [SFB 1430/1 2021]; [NW21-062B]; [EKFS-2014-A06]; [SFB1399]; [413326622]; [SFB1530] Funding text: We thank Alessandro Annibaldi for the scientific input and Christina Bebber and Silvia von Karstedt for their help with in vivo techniques. We also thank H. Gruell for their support with MRI imaging. PN is supported by E.I. Stiftung Koelner Krebsforschung and the Jurgen Manchot Stiftung. This work is supported by the Deutsche Forschungsgemeinschaft (DFG) (SFB1403 [414786233] to PN and WH, SFB1399 [413326622] to PN, WH, RHC, SML, GJ, BJ, BeF and LG, SFB1530 [455784452] to PN, WH, RHC, and LG, RE 2246/13-1, SFB 1430/1 2021 to RHC). The NRW Network consortium CANTAR (NW21-062B) to PN, WH, RHC, BJ and GJ. The German Ministry of Science and Education (BMBF), as part of the e:Med program (InCa, grant ID:01ZX1901) awarded to SML. The authors also acknowledge financial support from the National Laboratories Excellence program [under the National Tumour Biology Laboratory Project (NLP-17, 2022-2.1.1-NL-2022-00010] and the Hungarian Thematic Excellence Programme [TKP2021-EGA-44] to SL and TJ. RHC is supported by the Else Kroener-Fresenius Stiftung (EKFS-2014-A06, 2016_Kolleg.19), the Deutsche Krebshilfe (70115679, 1117240 and 70113041) and a Mildred Scheel Nachwuchszentrum Grant (Grant number 70113307), the German Ministry of Education and Research (BMBF e:Med 01ZX1303A), the Consortium HiRisk-HiGain ERAPERMED 2020-090 (01KU2104) and the MERCUR Foundation (IGNITE consortium, Ex-2021-0033). WH is supported by a Wellcome Trust Investigator Award (214342/Z/18/Z), an ERC Advanced Grant (294880), a Cancer Research UK programme grant (A27323), an MRC grant (MR/S00811X/1), an Alexander von Humboldt Professorship Award. BeF is supported by Deutsche Krebshilfe (70113041) and Mildred Scheel School of Oncology (70113307). MJ is supported by Ministerio de Ciencia, Innovacion y Universidades grant RTI2018-094533-A-I00; Ministerio de Ciencia e Innovacion, Proy. de Generacion del Conocimiento 2021 grant PID2021-128644OB-I0; Ministerio de Ciencia e Innovacion, Proyectos I + D + i Pruebas de Concepto 2022. grant PDC2022-133583-I00; and Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya 2021-SGR-00284. 0 false 2026-05-23T20:29:07.061+0000 2025-11-21T10:27:10.361+0000 2024-05-22T09:05:01.104+0000 true 10043337 Szokol Bálint /api/author/10043337 Author true 10043337 2025-11-24T12:44:10.649+0000 2025-11-24T12:44:10.649+0000 2024-06-09T19:25:55.404+0000 true 521 Szuper Admin /api/admin/521 Admin true true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Valdez Capuccino, L. CDK9 inhibition as an effective therapy for small cell lung cancer true true /api/journal/10015558 REVIEWED true false 10015558 false 10015558 true 2041-4889 2041-4889 Journal FOREIGN 15 5 345 345 12 2024 Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance to first-line therapy and alternative therapies are urgently required to overcome this resistance. In this study, we tested the efficacy of dinaciclib, an FDA-orphan drug and inhibitor of the cyclin-dependent kinase (CDK) 9, among other CDKs, in SCLC. Furthermore, we report on a newly developed, highly specific CDK9 inhibitor, VC-1, with tumour-killing activity in SCLC. CDK9 inhibition displayed high killing potential in a panel of mouse and human SCLC cell lines. Mechanistically, CDK9 inhibition led to a reduction in MCL-1 and cFLIP anti-apoptotic proteins and killed cells, almost exclusively, by intrinsic apoptosis. While CDK9 inhibition did not synergise with chemotherapy, it displayed high efficacy in chemotherapy-resistant cells. In vivo, CDK9 inhibition effectively reduced tumour growth and improved survival in both autochthonous and syngeneic SCLC models. Together, this study shows that CDK9 inhibition is a promising therapeutic agent against SCLC and could be applied to chemo-refractory or resistant SCLC. 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class="author-name" >Kleitke T. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10043337"><a href="/gui2/?type=authors&mode=browse&sel=10043337" target="_blank">Szokol B. (<span class="authorship-author-name">Szokol Bálint</span> <span class="authorAux-mtmt"> Gyógyszerkémia</span>) </a> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10083705"><a href="/gui2/?type=authors&mode=browse&sel=10083705" target="_blank">Svajda L. (<span class="authorship-author-name">Svajda Laura</span> <span class="authorAux-mtmt"> onkológia</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Martin F. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Bonechi F. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10061183"><a href="/gui2/?type=authors&mode=browse&sel=10061183" target="_blank">Krekó M. (<span class="authorship-author-name">Krekó Marcell</span> <span class="authorAux-mtmt"> gyógyszerészi kémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Gyógyszerésztudományi Kar">GYTK</span>/Gyógyszerészi Kémiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Azami S. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Montinaro A. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Wang Y. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Nikolov V. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kaiser L. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Bonasera D. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Saggau J. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Scholz T. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Schmitt A. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Beleggia F. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Reinhardt H. C. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >George J. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Liccardi G. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Walczak H. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10009941"><a href="/gui2/?type=authors&mode=browse&sel=10009941" target="_blank">Tóvári J. (<span class="authorship-author-name">Tóvári József</span> <span class="authorAux-mtmt"> Daganatbiológia, áttétképzés</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Brägelmann J. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Montero J. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Sos M. L. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10003054"><a href="/gui2/?type=authors&mode=browse&sel=10003054" target="_blank">Őrfi L. (<span class="authorship-author-name">Őrfi László</span> <span class="authorAux-mtmt"> Szerves- és Gyógyszerkémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Gyógyszerésztudományi Kar">GYTK</span>/Gyógyszerészi Kémiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Peltzer N. ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;34867519" target="_blank">CDK9 inhibition as an effective therapy for small cell lung cancer</a></div> <div> <span class="journal-title">CELL DEATH AND DISEASE</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/2041-4889">2041-4889</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/2041-4889">2041-4889</a>)</span>: <span class="journal-volume">15</span> <span class="journal-issue">5</span> <span class="page"> Paper 345. 12 p. </span> <span class="year">(2024)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1038/s41419-024-06724-4" target="_blank" href="https://doi.org/10.1038/s41419-024-06724-4"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001227916700005" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001227916700005"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85193695074" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85193695074"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="38769311" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=38769311&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cellular and Molecular Neuroscience&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cancer Research&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cell Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Immunology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 10</span> | Független: 8 | Függő: 2 | Nem jelölt: 0 | WoS jelölt: 8 | Scopus jelölt:&nbsp;5 | WoS/Scopus jelölt:&nbsp;8 | DOI jelölt:&nbsp;10 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;34867519&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 3 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 34867519</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (National Tumor Biology Laboratory project—2022-2.1.1-NL-2022-00010), Hungarian Thematic Excellence Program((TKP2021-EGA-44)), National Laboratories Excellence program (under the National Tumor Biology Laboratory Project(NLP-17) </div> <div class="lastModified">Utolsó módosítás: 2025.11.21. 11:27 Áncsán Gizella (SE admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: E.I. Stiftung Koelner Krebsforschung; Jurgen Manchot Stiftung; Deutsche Forschungsgemeinschaft (DFG) [455784452, ID:01ZX1901, 70115679, 1117240, 01ZX1303A, 2020-090, NLP-17, 2022-2.1.1-NL-2022-00010]; The NRW Network consortium CANTAR [TKP2021-EGA-44]; German Ministry of Science and Education (BMBF); National Laboratories Excellence program [under the National T...</pre> </div></div>