{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:12:35Z","timestamp":1785420755976,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union, OPZUID","award":["STIM-00107"],"award-info":[{"award-number":["STIM-00107"]}]},{"award":["STIM-00107"],"award-info":[{"award-number":["STIM-00107"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Catharina Research fund","award":["2022-3"],"award-info":[{"award-number":["2022-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Treatment options for recurrent ovarian cancer (OC) are limited, leading to poor prognosis. Targeting tumor-promoting signaling transduction pathways (STPs), such as Hedgehog (HH) and Phosphoinositide-3-kinase (PI3K) STPs, might be an option for treatment. This study evaluates the efficacy of itraconazole as a targeted treatment in HH and\/or PI3K active recurrent OC. Methods: We assessed HH and PI3K STP activity in recurrent OC patients. If activity was aberrantly high in either STP, patients received itraconazole treatment, which has been shown to inhibit both HH and PI3K pathways. The primary objective is to compare progression-free survival (PFS) on itraconazole therapy (PFS2) to the PFS on therapy prior to enrolment (PFS1). A PFS2\/PFS1 \u2265 1.0 was considered successful. Secondary objectives included side effects, best overall response, one-year survival, and CA125 levels, though this was not a secondary endpoint. Results: Of sixteen patients with successful STP analysis, 93% were eligible for itraconazole therapy. Nine patients started treatment, with a mean duration of 55 days. None achieved a PFS2\/PFS1 ratio \u2265 1.0 (mean 0.26, range 0.1\u20130.7). One patient had radiologically stable disease, while the others experienced disease progression. Side effects were mostly limited to grade 1\u20132, including fatigue, nausea, dysgeusia, dyspnea, cough, vertigo, and edema. No grade \u2265 3 adverse effects were linked to treatment. One-year survival was 22%. CA125 levels did not correlate with the treatment outcome, but increased rapidly after ceasing treatment. Conclusions: Itraconazole monotherapy for recurrent HH and\/or PI3K aberrantly active OC is an ineffective treatment. While CA125 did not correlate with treatment outcome, the rapid increase in CA125 after therapy cessation suggests tumor inhibitory effects.<\/jats:p>","DOI":"10.3390\/cancers18091468","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:15:02Z","timestamp":1777853702000},"page":"1468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Itraconazole in the Treatment of Aberrantly Active Hedgehog and\/or PI3K Recurrent Ovarian Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8108-6659","authenticated-orcid":false,"given":"Cynthia S. E.","family":"Hendrikse","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands"},{"name":"GROW School for Oncology and Reproduction, Maastricht University, 6211 LK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-966X","authenticated-orcid":false,"given":"Noortje","family":"Voeten","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5099-7473","authenticated-orcid":false,"given":"Phyllis","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0971-1859","authenticated-orcid":false,"given":"Huberdina P. M.","family":"Smedts","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Amphia Hospital, 4818 CK Breda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-3638","authenticated-orcid":false,"given":"Hans M.","family":"Westgeest","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Amphia Hospital, 4818 CK Breda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Eurofins PAMM, 5623 EJ Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-0947","authenticated-orcid":false,"given":"Roy I.","family":"Lalisang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Maastricht University Hospital, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6782-6291","authenticated-orcid":false,"given":"Birgit E. P. J.","family":"Vriens","sequence":"additional","affiliation":[{"name":"Department of Oncology, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M. J.","family":"Thijs","sequence":"additional","affiliation":[{"name":"Department of Oncology, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrina","family":"Lambrechts","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Maastricht University Hospital, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-8495","authenticated-orcid":false,"given":"Ruud L. M.","family":"Bekkers","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands"},{"name":"GROW School for Oncology and Reproduction, Maastricht University, 6211 LK Maastricht, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Radboudumc, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0487-0631","authenticated-orcid":false,"given":"Jurgen M. J.","family":"Piek","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Catharina Cancer Institute, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/ijgo.13878","article-title":"Cancer of the ovary, fallopian tube, and peritoneum: 2021 update","volume":"155","author":"Berek","year":"2021","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101450","DOI":"10.1016\/j.gore.2024.101450","article-title":"Targeted therapy in high grade serous ovarian Cancer: A literature review","volume":"54","author":"Dinkins","year":"2024","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1200\/JCO.2013.51.4489","article-title":"Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial","volume":"32","author":"Hilpert","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/S1470-2045(15)00188-6","article-title":"Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): A multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial","volume":"16","author":"Delord","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1158\/2159-8290.CD-16-1396","article-title":"High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial","volume":"7","author":"Massard","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000479006","article-title":"Ovarian Cancer: A Heterogeneous Disease","volume":"85","author":"Kossai","year":"2018","journal-title":"Pathobiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cancergen.2019.11.008","article-title":"Molecular profiling of gynecologic cancers for treatment and management of disease\u2013demonstrating clinical significance using the AMP\/ASCO\/CAP guidelines for interpretation and reporting of somatic variants","volume":"242","author":"Nie","year":"2020","journal-title":"Cancer Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/cncr.34661","article-title":"Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma","volume":"129","author":"Hendrikse","year":"2023","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, Y., Yang, Y., Yang, J., Zhao, X., and Wei, X. (2020). Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00758"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"van de Stolpe, A., Verhaegh, W., Blay, J.Y., Ma, C.X., Pauwels, P., Pegram, M., Prenen, H., De Ruysscher, D., Saba, N.F., and Slovin, S.F. (2020). RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.598118"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1158\/0008-5472.CAN-13-2515","article-title":"Selection of personalized patient therapy through the use of knowledge-based computational models that identify tumor-driving signal transduction pathways","volume":"74","author":"Verhaegh","year":"2014","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1016\/j.ajpath.2018.05.020","article-title":"Assessment of Functional Phosphatidylinositol 3-Kinase Pathway Activity in Cancer Tissue Using Forkhead Box-O Target Gene Expression in a Knowledge-Based Computational Model","volume":"188","author":"Hornsveld","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1038\/s41598-018-38179-x","article-title":"Enabling precision medicine by unravelling disease pathophysiology: Quantifying signal transduction pathway activity across cell and tissue types","volume":"9","author":"Holtzer","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_15","unstructured":"(2026, February 11). Cell Signaling Pathways. Available online: https:\/\/www.innosignbio.com\/products\/science\/."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Inda, M.A., van Swinderen, P., van Brussel, A., Moelans, C.B., Verhaegh, W., van Zon, H., den Biezen, E., Bikker, J.W., van Diest, P.J., and van de Stolpe, A. (2021). Heterogeneity in Signaling Pathway Activity within Primary and between Primary and Metastatic Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13061345"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sieuwerts, A.M., Inda, M.A., Smid, M., van Ooijen, H., van de Stolpe, A., Martens, J.W.M., and Verhaegh, W.F.J. (2020). ER and PI3K Pathway Activity in Primary ER Positive Breast Cancer Is Associated with Progression-Free Survival of Metastatic Patients under First-Line Tamoxifen. Cancers, 12.","DOI":"10.3390\/cancers12040802"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1002\/ijc.32795","article-title":"Prediction of clinical benefit from androgen deprivation therapy in salivary duct carcinoma patients","volume":"146","author":"Verhaegh","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cell.2018.03.035","article-title":"Oncogenic Signaling Pathways in The Cancer Genome Atlas","volume":"173","author":"Mina","year":"2018","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.canep.2015.11.014","article-title":"Hedgehog signaling pathway as a therapeutic target for ovarian cancer","volume":"40","author":"Li","year":"2016","journal-title":"Cancer Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/carcin\/bgn230","article-title":"Aberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiation","volume":"30","author":"Liao","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.semcancer.2019.05.012","article-title":"Role of the PI3K\/AKT\/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance","volume":"59","author":"Ediriweera","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102021","DOI":"10.1016\/j.ctrv.2020.102021","article-title":"Targeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer","volume":"86","author":"Huang","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ygyno.2022.01.027","article-title":"Signal transduction pathway activity in high-grade serous carcinoma, its precursors and Fallopian tube epithelium","volume":"165","author":"Uittenboogaard","year":"2022","journal-title":"Gynecol. Oncol."},{"key":"ref_25","first-page":"2481","article-title":"Impact of combination chemotherapy with itraconazole on survival of patients with refractory ovarian cancer","volume":"34","author":"Tsubamoto","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_26","first-page":"2007","article-title":"Impact of combination chemotherapy with itraconazole on survival for patients with recurrent or persistent ovarian clear cell carcinoma","volume":"34","author":"Tsubamoto","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1634\/theoncologist.2012-314","article-title":"Repurposing itraconazole as a treatment for advanced prostate cancer: A noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer","volume":"18","author":"Antonarakis","year":"2013","journal-title":"Oncologist"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1016\/j.clgc.2018.09.013","article-title":"Itraconazole as a Noncastrating Treatment for Biochemically Recurrent Prostate Cancer: A Phase 2 Study","volume":"17","author":"Lee","year":"2019","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1158\/1535-7163.MCT-20-0638","article-title":"Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2\/AKT Signaling Pathway","volume":"20","author":"Zhang","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.3892\/ol.2017.6569","article-title":"Repurposing itraconazole for the treatment of cancer","volume":"14","author":"Pounds","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e23170","DOI":"10.1016\/j.heliyon.2023.e23170","article-title":"Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol","volume":"10","author":"Hendrikse","year":"2024","journal-title":"Heliyon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2105\/AJPH.94.3.361","article-title":"Improving the reporting quality of nonrandomized evaluations of behavioral and public health interventions: The TREND statement","volume":"94","author":"Lyles","year":"2004","journal-title":"Am. J. Public Health"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/path.1000","article-title":"Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer","volume":"195","author":"Piek","year":"2001","journal-title":"J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/aogs.14306","article-title":"Cyclic activity of signal transduction pathways in fimbrial epithelium of the human fallopian tube","volume":"101","author":"Uittenboogaard","year":"2022","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1086\/605499","article-title":"Toxicodynamics of itraconazole: Implications for therapeutic drug monitoring","volume":"49","author":"Lestner","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101035","DOI":"10.1016\/j.gore.2022.101035","article-title":"The progression-free survival ratio as outcome measure in recurrent ovarian carcinoma patients: Current and future perspectives","volume":"42","author":"Wilting","year":"2022","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Besheir, A.E.S., El-Hagar, S.M., Tawfik, H.A., and Mostafa, T.M. (2025). A Novel Approach to Reducing Chemoresistance in Advanced Ovarian Cancer: The Effect of Itraconazole-A Single-Institution Randomized Placebo-Controlled Trial. Curr. Oncol., 33.","DOI":"10.3390\/curroncol33010021"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110661","DOI":"10.1016\/j.biopha.2020.110661","article-title":"Itraconazole exerts anti-liver cancer potential through the Wnt, PI3K\/AKT\/mTOR, and ROS pathways","volume":"131","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28510","DOI":"10.18632\/oncotarget.15324","article-title":"Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K\/mTOR signaling pathways","volume":"8","author":"Liang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ygyno.2023.01.038","article-title":"The potential of RAS\/RAF\/MEK\/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis","volume":"171","author":"Hendrikse","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1016\/j.clgc.2013.11.015","article-title":"High-dose itraconazole as a noncastrating therapy for a patient with biochemically recurrent prostate cancer","volume":"12","author":"Suzman","year":"2014","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"188503","DOI":"10.1016\/j.bbcan.2021.188503","article-title":"Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer","volume":"1875","author":"Zhang","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Charkhchi, P., Cybulski, C., Gronwald, J., Wong, F.O., Narod, S.A., and Akbari, M.R. (2020). CA125 and Ovarian Cancer: A Comprehensive Review. Cancers, 12.","DOI":"10.3390\/cancers12123730"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nguyen, N.M., and Cho, J. (2022). Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031733"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41392-021-00828-5","article-title":"Targeting PI3K\/Akt signal transduction for cancer therapy","volume":"6","author":"He","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e000573","DOI":"10.1136\/bmjonc-2024-000573","article-title":"Thirty years from FDA approval of pegylated liposomal doxorubicin (Doxil\/Caelyx): An updated analysis and future perspective","volume":"4","author":"Gabizon","year":"2025","journal-title":"BMJ Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jconrel.2020.10.014","article-title":"Carrier-free nanodrugs for safe and effective cancer treatment","volume":"329","author":"Karaosmanoglu","year":"2021","journal-title":"J. Control. Release"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/9\/1468\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:22:40Z","timestamp":1777854160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/9\/1468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,2]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cancers18091468"],"URL":"https:\/\/doi.org\/10.3390\/cancers18091468","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,2]]}}}