https://m2.mtmt.hu/ hun 2026-09-22 18:16 JournalArticle 36234471 ADMIN_APPROVED true Funding Agency and Grant Number: Hungarian Scientific Research Grant of the National Research, Development and Innovation (NRDI) Office Fund of the Ministry of Culture and Innovation under the National Laboratories Program (National Tumour Biology Laboratory) [2022-2.1.1-NL-2022-00010]; Hungarian Thematic Excellence Program [TKP2021-EGA/TKP2021-NVA/TKP2021-NKTA]; National Research, Development and Innovation (NRDI) Office Fund [NRDI NKFI-FK135065]; New National Excellence Program of the Ministry of Human Capacities [UNKP-23-5-SE-4]; Bolyai Research Fellowship of the Hungarian Academy of Sciences [BO/00092/21] Funding text: Hungarian Scientific Research Grant of the National Research, Development and Innovation (NRDI) Office Fund of the Ministry of Culture and Innovation under the National Laboratories Program (National Tumour Biology Laboratory (2022-2.1.1-NL-2022-00010)) grant agreements (A.P. and H.B.) and the Hungarian Thematic Excellence Program (TKP2021-EGA/TKP2021-NVA/TKP2021-NKTA, MOLORKIV (A.P.). National Research, Development and Innovation (NRDI) Office Fund NRDI NKFI-FK135065 (H.B.). The New National Excellence Program of the Ministry of Human Capacities UNKP-23-5-SE-4 (H.B.). Bolyai Research Fellowship of the Hungarian Academy of Sciences BO/00092/21 (H.B.). 0 false 2026-09-13T20:35:42.733+0000 2026-04-28T12:09:50.361+0000 2025-07-08T07:09:35.947+0000 true 10015206 Áncsán Gizella /api/admin/10015206 Admin true 10015206 2026-04-28T12:09:50.197+0000 2026-04-21T11:32:51.589+0000 true 10101957 Pirmann Tamás /api/admin/10101957 Admin true Admin 10013962 /api/admin/10013962 Vasvari Lilian true 10013962 true 2026-06-15T18:02:43.108+0000 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 Butz, Henriett Defactinib in Combination with Mitotane Can Be an Effective Treatment in Human Adrenocortical Carcinoma true true /api/journal/10003252 REVIEWED true false 10003252 false 10003252 true 1661-6596 1422-0067 Journal FOREIGN 26 13 6539 6539 17 2025 Adrenocortical carcinoma (ACC) is an aggressive cancer with a poor prognosis. Mitotane, the only FDA-approved treatment for ACC, targets adrenocortical cells and reduces cortisol levels. Although it remains the cornerstone of systemic therapy, its overall impact on long-term outcomes is still a matter of ongoing clinical debate. Drug repurposing is a cost-effective way to identify new therapies, and defactinib, currently in clinical trials as part of combination therapies for various solid tumours, may enhance ACC treatment. We aimed to assess its efficacy in combination with mitotane. We tested the combination of mitotane and defactinib in H295R, SW13, and mitotane-sensitive and -resistant HAC15 cells, using functional assays, transcriptomic profiling, 2D and 3D cultures, bioprinted tissues, and xenografts. We assessed drug interactions with NMR and toxicity in vivo, as mitotane and defactinib have never been previously administered together. Genomic data from 228 human ACC and 158 normal adrenal samples were also analysed. Transcriptomic analysis revealed dysregulation of focal adhesion along with mitotane-related pathways. Focal adhesion kinase (FAK) signalling was enhanced in ACC compared to normal adrenal glands, with PTK2 (encoding FAK) upregulated in 44% of tumour samples due to copy number alterations. High FAK signature scores correlated with worse survival outcomes. FAK inhibition by defactinib, both alone and in combination with mitotane, showed effective anti-tumour activity in vitro. No toxicity or drug—drug interactions were observed in vivo. Combination treatment significantly reduced tumour volume and the number of macrometastases compared to those in the mitotane and control groups, with defactinib-treated tumours showing increased necrosis in xenografts. Defactinib combined with conventionally used mitotane shows promise as a novel combination therapy for ACC and warrants further investigation. Funding 2055195 /api/funding/2055195 false true Funding 2055196 /api/funding/2055196 false true Funding 2055197 /api/funding/2055197 false true Funding 2055198 /api/funding/2055198 false true Funding 2055199 /api/funding/2055199 false true Funding 2055200 /api/funding/2055200 false true Funding 2055201 /api/funding/2055201 false true Funding 2055202 /api/funding/2055202 false true true INTERNATIONAL 2025 true true true false true false GOLD 2026-09-13 true https://doi.org/10.3390/ijms26136539 1 0 1 1 0 1 1 1 1 1 1 1 1 1 0 0 1 1 1 1 0 8 8 Folyóiratcikk Journal Article 24 1 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2026 0 1 1 1 1 D1 false false false false 2025-07-13T06:23:47.618+0000 Belgyógyászati és Onkológiai Klinika (SE / AOK / K); Endokrinológiai Tanszék (SE / AOK / K / BOK); HUN-REN-ONKOL-TTK-HCEMM Onkogenomikai Kutatócso... (OOI); Laboratóriumi Medicina Intézet (SE / AOK / I); Országos Onkológiai Intézet; Patológiai és Kísérleti Rákkutató Intézet (SE / AOK / I) 17 58 6 19 0 true 10013962 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 127171606 /api/authorship/127171606 1 0.053 true false true Author 10020420 /api/author/10020420 Butz Henriett true 10020420 true Butz Henriett true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171607 /api/authorship/127171607 2 0.05263158 false false false Author 10045334 /api/author/10045334 Pongor Lőrinc true 10045334 true Pongor Lőrinc true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171608 /api/authorship/127171608 3 0.053 false false false Author 10071844 /api/author/10071844 Krokker Lilla true true Krokker Lilla true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171609 /api/authorship/127171609 4 0.053 false false false Author 10065387 /api/author/10065387 Szabó Borbála true true Szabó Borbála true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171610 /api/authorship/127171610 5 0.053 false false false Author 10024599 /api/author/10024599 Dezső Katalin true 10024599 true Dezső Katalin true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171611 /api/authorship/127171611 6 0.053 false false false Author 10065723 /api/author/10065723 Dankó Titanilla true true Dankó Titanilla true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171612 /api/authorship/127171612 7 0.053 false false false Author 10000745 /api/author/10000745 Sebestyén Anna true 10000745 true Sebestyén Anna true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171613 /api/authorship/127171613 8 0.053 false false false Author 10074525 /api/author/10074525 Sztankovics Dániel true true Sztankovics Dániel true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171614 /api/authorship/127171614 9 0.053 false false false Author 10009941 /api/author/10009941 Tóvári József true 10009941 true Tóvári József true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171615 /api/authorship/127171615 10 0.053 false false false Author 10079803 /api/author/10079803 Surguta Sára Eszter true true Surguta Sára Eszter true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171616 /api/authorship/127171616 11 0.053 false false false Author 10025130 /api/author/10025130 Likó István true 10025130 true Likó István true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 127171617 /api/authorship/127171617 12 0.053 false false false 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src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10020420"><a href="/gui2/?type=authors&mode=browse&sel=10020420" target="_blank">Butz Henriett ✉ (<span class="authorship-author-name">Butz Henriett</span> <span class="authorAux-mtmt"> orvostudomány</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Laboratóriumi Medicina Intézet; <span title="Országos Onkológiai Intézet">OOI</span>/HUN-REN-ONKOL-TTK-HCEMM Onkogenomikai Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10045334"><a href="/gui2/?type=authors&mode=browse&sel=10045334" target="_blank">Pongor Lőrinc (<span class="authorship-author-name">Pongor Lőrinc</span> <span class="authorAux-mtmt"> Bioinformatika</span>) </a> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10071844"><a href="/gui2/?type=authors&mode=browse&sel=10071844" target="_blank">Krokker Lilla (<span class="authorship-author-name">Krokker Lilla</span> <span class="authorAux-mtmt"> Orvostudomány</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Laboratóriumi Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10065387"><a href="/gui2/?type=authors&mode=browse&sel=10065387" target="_blank">Szabó Borbála (<span class="authorship-author-name">Szabó Borbála</span> <span class="authorAux-mtmt"> Endokrinológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Laboratóriumi Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10024599"><a href="/gui2/?type=authors&mode=browse&sel=10024599" target="_blank">Dezső Katalin (<span class="authorship-author-name">Dezső Katalin</span> <span class="authorAux-mtmt"> Patológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Patológiai és Kísérleti Rákkutató Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10065723"><a href="/gui2/?type=authors&mode=browse&sel=10065723" target="_blank">Dankó Titanilla (<span class="authorship-author-name">Dankó Titanilla</span> <span class="authorAux-mtmt"> Tumorbiológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Patológiai és Kísérleti Rákkutató Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000745"><a href="/gui2/?type=authors&mode=browse&sel=10000745" target="_blank">Sebestyén Anna (<span class="authorship-author-name">Sebestyén Anna</span> <span class="authorAux-mtmt"> Tumorbiológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Patológiai és Kísérleti Rákkutató Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10074525"><a href="/gui2/?type=authors&mode=browse&sel=10074525" target="_blank">Sztankovics Dániel (<span class="authorship-author-name">Sztankovics Dániel</span> <span class="authorAux-mtmt"> Onkológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Patológiai és Kísérleti Rákkutató Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10009941"><a href="/gui2/?type=authors&mode=browse&sel=10009941" target="_blank">Tóvári József (<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" mtid="10079803"><a href="/gui2/?type=authors&mode=browse&sel=10079803" target="_blank">Surguta Sára Eszter (<span class="authorship-author-name">Surguta Sára Eszter</span> <span class="authorAux-mtmt"> Kísérletes Farmakológia</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10025130"><a href="/gui2/?type=authors&mode=browse&sel=10025130" target="_blank">Likó István (<span class="authorship-author-name">Likó István</span> <span class="authorAux-mtmt"> Bioinformatika-Molekuláris biológia</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet; <span title="Országos Onkológiai Intézet">OOI</span>/HUN-REN-ONKOL-TTK-HCEMM Onkogenomikai Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10058121"><a href="/gui2/?type=authors&mode=browse&sel=10058121" target="_blank">Mészáros Katalin (<span class="authorship-author-name">Mészáros Katalin</span> <span class="authorAux-mtmt"> orvosi laboratóriumi diagnosztika</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Laboratóriumi Medicina Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Deák Andrea </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10101286"><a href="/gui2/?type=authors&mode=browse&sel=10101286" target="_blank">Fekete Fanni (<span class="authorship-author-name">Fekete Fanni</span> <span class="authorAux-mtmt"> biológus</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Vida Ramóna </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10023798"><a href="/gui2/?type=authors&mode=browse&sel=10023798" target="_blank">Báthory-Fülöp László (<span class="authorship-author-name">Báthory-Fülöp László</span> <span class="authorAux-mtmt"> élettan</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10062288"><a href="/gui2/?type=authors&mode=browse&sel=10062288" target="_blank">Tóth Erika (<span class="authorship-author-name">Tóth Erika</span> <span class="authorAux-mtmt"> patológia</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000070"><a href="/gui2/?type=authors&mode=browse&sel=10000070" target="_blank">Igaz Péter (<span class="authorship-author-name">Igaz Péter</span> <span class="authorAux-mtmt"> belgyógyászat, endokrinológia, klinikai molekul...</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/Belgyógyászati és Onkológiai Klinika; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/<span title="Belgyógyászati és Onkológiai Klinika">BOK</span>/Endokrinológiai Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10001006"><a href="/gui2/?type=authors&mode=browse&sel=10001006" target="_blank">Patócs Attila ✉ (<span class="authorship-author-name">Patócs Attila Balázs</span> <span class="authorAux-mtmt"> Orvostudomány</span>) </a> </span> <span class="author-affil">Országos Onkológiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Laboratóriumi Medicina Intézet; <span title="Országos Onkológiai Intézet">OOI</span>/HUN-REN-ONKOL-TTK-HCEMM Onkogenomikai Kutatócsoport</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;36234471" target="_blank">Defactinib in Combination with Mitotane Can Be an Effective Treatment in Human Adrenocortical Carcinoma</a></div> <div> <span class="journal-title">INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1661-6596">1661-6596</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1422-0067">1422-0067</a>)</span>: <span class="journal-volume">26</span> <span class="journal-issue">13</span> <span class="page"> Paper 6539. 17 p. </span> <span class="year">(2025)</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_GOLD" title=" Gold "> <a style="color:blue" title="10.3390/ijms26136539" target="_blank" href="https://doi.org/10.3390/ijms26136539"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001526383000001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001526383000001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="105010314190" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-105010314190"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="40650315" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=40650315&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Inorganic Chemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Organic Chemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Spectroscopy&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Catalysis&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Computer Science Applications&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Physical and Theoretical Chemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q2</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: 1</span> | Független: 1 | Függő: 0 | Nem jelölt: 0 | WoS jelölt: 1 | Scopus jelölt:&nbsp;1 | WoS/Scopus jelölt:&nbsp;1 | DOI jelölt:&nbsp;1 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;36234471&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 8 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 36234471</span> | <span class="status-data status-ADMIN_APPROVED"> Admin láttamozott </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">WOS TAGGED</span> </div> <div class="funder"> (National Tumor Biology Laboratory (2022–2.1.1-NL-2022-00010))), (TKP2021-EGA), (TKP2021-NVA), (TKP2021-NKTA), (MOLORKIV), (NRDI NKFI-FK135065), (ÚNKP-23-5-SE-4), (BO/00092/21) Támogató: MTA Bolyai pályázat </div> <div class="lastModified">Utolsó módosítás: 2026.04.28. 14:09 Áncsán Gizella (SE admin) </div> <div class="lockedBy">Központi kezelésű 2026.06.15. 20:02 Vasvari Lilian (MTMT Központ, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: Hungarian Scientific Research Grant of the National Research, Development and Innovation (NRDI) Office Fund of the Ministry of Culture and Innovation under the National Laboratories Program (National Tumour Biology Laboratory) [2022-2.1.1-NL-2022-00010]; Hungarian Thematic Excellence Program [TKP2021-EGA/TKP2021-NVA/TKP2021-NKTA]; National Research, Development ...</pre> </div></div>