{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T07:30:02Z","timestamp":1786433402492,"version":"build-2736575974"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The International Journal of Biochemistry & Cell Biology"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.biocel.2026.106987","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T18:51:19Z","timestamp":1781463079000},"page":"106987","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Targeting PI3K\u03b3\/AKT1-OCT4\/SOX2 axis with eganelisib suppresses tumor growth and prevents ovarian failure in malignant ovarian germ cell tumors"],"prefix":"10.1016","volume":"199","author":[{"given":"Yanning","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghui","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-3472","authenticated-orcid":false,"given":"Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.biocel.2026.106987_bib1","doi-asserted-by":"crossref","first-page":"17561","DOI":"10.1007\/s00210-025-04264-y","article-title":"Piceatannol protects against cisplatin-induced ovarian toxicity in rats via modulation of PTEN\/PI3 K\/AKT axis","volume":"398","author":"Alorabi","year":"2025","journal-title":"Naunyn Schmiede Arch. Pharmacol."},{"issue":"7","key":"10.1016\/j.biocel.2026.106987_bib2","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S2213-8587(15)00039-X","article-title":"Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults","volume":"3","author":"Anderson","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"1","key":"10.1016\/j.biocel.2026.106987_bib3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13048-025-01643-0","article-title":"Zishen Yutai pill ameliorates ovarian reserve by mediating PI3K-Akt pathway and apoptosis level in ovary","volume":"18","author":"Chen","year":"2025","journal-title":"J. Ovarian Res."},{"issue":"1","key":"10.1016\/j.biocel.2026.106987_bib4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13287-025-04229-1","article-title":"OCT4 translationally promotes AKT signaling as an RNA-binding protein in stressed pluripotent stem cells","volume":"16","author":"Chen","year":"2025","journal-title":"Stem Cell. Res. Ther."},{"issue":"2","key":"10.1016\/j.biocel.2026.106987_bib5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s12519-009-0020-7","article-title":"Disorders of sex development: update on the genetic background, terminology and risk for the development of germ cell tumors","volume":"5","author":"Cools","year":"2009","journal-title":"World J. Pediatr."},{"issue":"11","key":"10.1016\/j.biocel.2026.106987_bib6","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22115982","article-title":"To be or not to be a germ cell: the extragonadal germ cell tumor paradigm","volume":"22","author":"De Felici","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"7629","key":"10.1016\/j.biocel.2026.106987_bib7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature20554","article-title":"Overcoming resistance to checkpoint blockade therapy by targeting PI3Kgamma in myeloid cells","volume":"539","author":"De Henau","year":"2016","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.biocel.2026.106987_bib8","doi-asserted-by":"crossref","DOI":"10.3802\/jgo.2025.36.e108","article-title":"Malignant germ cells tumor of the ovary","volume":"36","author":"De Maria","year":"2025","journal-title":"J. Gynecol. Oncol."},{"issue":"9","key":"10.1016\/j.biocel.2026.106987_bib9","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1093\/humrep\/dev128","article-title":"Live birth after autograft of ovarian tissue cryopreserved during childhood","volume":"30","author":"Demeestere","year":"2015","journal-title":"Hum. Reprod."},{"issue":"2","key":"10.1016\/j.biocel.2026.106987_bib10","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.fertnstert.2015.10.026","article-title":"Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval","volume":"105","author":"Doyle","year":"2016","journal-title":"Fertil. Steril."},{"issue":"1","key":"10.1016\/j.biocel.2026.106987_bib11","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/s13048-024-01545-7","article-title":"MSCs-derived EVs protect against chemotherapy-induced ovarian toxicity: role of PI3K\/AKT\/mTOR axis","volume":"17","author":"Elsherbiny","year":"2024","journal-title":"J. Ovarian Res."},{"issue":"9","key":"10.1016\/j.biocel.2026.106987_bib12","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1021\/acsmedchemlett.6b00238","article-title":"Discovery of a selective phosphoinositide-3-kinase (PI3K)-gamma inhibitor (IPI-549) as an immuno-oncology clinical candidate","volume":"7","author":"Evans","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"issue":"3","key":"10.1016\/j.biocel.2026.106987_bib13","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/humrep\/deac249","article-title":"Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation","volume":"38","author":"Fraison","year":"2023","journal-title":"Hum. Reprod."},{"issue":"6","key":"10.1016\/j.biocel.2026.106987_bib14","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aav9960","article-title":"Mechanical stress accompanied with nuclear rotation is involved in the dormant state of mouse","volume":"5","author":"Go Nagamatsu","year":"2019","journal-title":"Sci. Adv."},{"issue":"5","key":"10.1016\/j.biocel.2026.106987_bib15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humupd\/dmae020","article-title":"Ovarian microenvironment: challenges and opportunities in protecting against chemotherapyassociated ovarian damage","volume":"30","author":"Guo","year":"2024","journal-title":"Human. Reprod. Update"},{"issue":"185","key":"10.1016\/j.biocel.2026.106987_bib16","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3005402","article-title":"Cyclophosphamide triggers follicle activation and \"burnout\"; AS101 prevents follicle loss and preserves fertility","volume":"5","author":"Kalich-Philosoph","year":"2013","journal-title":"Sci. Transl. Med."},{"issue":"8","key":"10.1016\/j.biocel.2026.106987_bib17","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/nm.2889","article-title":"Cisplatin-induced primordial follicle oocyte killing and loss of fertility are not prevented by imatinib","volume":"18","author":"Kerr","year":"2012","journal-title":"Nat. Med."},{"key":"10.1016\/j.biocel.2026.106987_bib18","doi-asserted-by":"crossref","first-page":"7769","DOI":"10.1038\/ncomms8769","article-title":"PI3K\/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis","volume":"6","author":"Lee","year":"2015","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.biocel.2026.106987_bib19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12943-024-02072-1","article-title":"Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions","volume":"23","author":"Li","year":"2024","journal-title":"Mol. Cancer"},{"issue":"4","key":"10.1016\/j.biocel.2026.106987_bib20","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.molcel.2012.08.030","article-title":"Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells","volume":"48","author":"Lin","year":"2012","journal-title":"Mol. Cell."},{"issue":"2","key":"10.1016\/j.biocel.2026.106987_bib21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/dnares\/dsy042","article-title":"Molecular characteristics of early-stage female germ cells revealed by RNA sequencing of low-input cells and analysis of genome-wide DNA methylation","volume":"26","author":"Ma","year":"2019","journal-title":"DNA Res."},{"key":"10.1016\/j.biocel.2026.106987_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.112993","article-title":"Dingkun Pill replenishes diminished ovarian reserve through the PI3K\/AKT\/mTOR signaling pathway in TWP-induced mice","volume":"262","author":"Ma","year":"2020","journal-title":"J. Ethnopharmacol."},{"issue":"1","key":"10.1016\/j.biocel.2026.106987_bib23","doi-asserted-by":"crossref","DOI":"10.3390\/cells9010200","article-title":"Crosstalk between PTEN\/PI3K\/Akt signalling and DNA damage in the oocyte: implications for primordial follicle activation, oocyte quality and ageing","volume":"9","author":"Maidarti","year":"2020","journal-title":"Cells"},{"issue":"23","key":"10.1016\/j.biocel.2026.106987_bib24","doi-asserted-by":"crossref","first-page":"3748","DOI":"10.1080\/15384101.2015.1104444","article-title":"Novel AKT phosphorylation sites identified in the pluripotency factors OCT4, SOX2 and KLF4","volume":"14","author":"Malak","year":"2015","journal-title":"Cell. Cycle"},{"issue":"5","key":"10.1016\/j.biocel.2026.106987_bib25","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/his.14609","article-title":"Key changes to the World Health Organization (WHO) classification of female genital tumours introduced in the 5th edition (2020)","volume":"80","author":"McCluggage","year":"2022","journal-title":"Histopathology"},{"key":"10.1016\/j.biocel.2026.106987_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.108963","article-title":"Protective properties of glycogen synthase kinase-3 inhibition against doxorubicin-induced oxidative damage to mouse ovarian reserve","volume":"116","author":"Niringiyumukiza","year":"2019","journal-title":"Biomed. Pharmacother."},{"issue":"Pt 1","key":"10.1016\/j.biocel.2026.106987_bib27","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.semcancer.2019.08.007","article-title":"SOX2 in development and cancer biology","volume":"67","author":"Novak","year":"2020","journal-title":"Semin. Cancer Biol."},{"issue":"8","key":"10.1016\/j.biocel.2026.106987_bib28","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-009160","article-title":"Eganelisib combined with immune checkpoint inhibitor therapy and chemotherapy in frontline metastatic triple-negative breast cancer triggers macrophage reprogramming, immune activation and extracellular matrix reorganization in the tumor microenvironment","volume":"12","author":"O'Connell","year":"2024","journal-title":"J. Immunother. Cancer"},{"issue":"12","key":"10.1016\/j.biocel.2026.106987_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e32802","article-title":"Investigating the potential role of alpha-SNAP in preventing chemotherapy-induced ovarian dysfunction: insights from cellular and animal models","volume":"10","author":"Qin","year":"2024","journal-title":"Heliyon"},{"issue":"12","key":"10.1016\/j.biocel.2026.106987_bib30","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph20126089","article-title":"Clinical challenges in the management of malignant ovarian germ cell tumours","volume":"20","author":"Saani","year":"2023","journal-title":"Int. J. Environ. Res. Public. Health"},{"issue":"6","key":"10.1016\/j.biocel.2026.106987_bib31","article-title":"Embryonic stem cell transcription Stem Cell TF Signatures in GCTs","volume":"31","author":"Sandro Santagata","year":"2007"},{"issue":"7","key":"10.1016\/j.biocel.2026.106987_bib32","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/s10815-018-1180-y","article-title":"Biomechanics and mechanical signaling in the ovary: a systematic review","volume":"35","author":"Shah","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"issue":"25","key":"10.1016\/j.biocel.2026.106987_bib33","doi-asserted-by":"crossref","first-page":"12321","DOI":"10.1073\/pnas.1817223116","article-title":"Hypoxia induces the dormant state in oocytes through expression of Foxo3","volume":"116","author":"Shimamoto","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"6","key":"10.1016\/j.biocel.2026.106987_bib34","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/humupd\/dmz027","article-title":"Ovarian damage from chemotherapy and current approaches to its protection","volume":"25","author":"Spears","year":"2019","journal-title":"Hum. Reprod. Update"},{"issue":"6","key":"10.1016\/j.biocel.2026.106987_bib35","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/onco.13675","article-title":"Can some anticancer treatments preserve the ovarian reserve?","volume":"26","author":"Vallet","year":"2021","journal-title":"Oncologist"},{"issue":"7","key":"10.1016\/j.biocel.2026.106987_bib36","article-title":"Urolithin a protects ovarian reserve via inhibiting PI3K\/Akt signaling and preventing chemotherapy-induced follicle apoptosis","volume":"14","author":"Wang","year":"2025","journal-title":"Biol. (Basel)"},{"issue":"5","key":"10.1016\/j.biocel.2026.106987_bib37","doi-asserted-by":"crossref","first-page":"R177","DOI":"10.1530\/EJE-20-1178","article-title":"THERAPY OF ENDOCRINE DISEASE: novel protection and treatment strategies for chemotherapy-associated ovarian damage","volume":"184","author":"Xiong","year":"2021","journal-title":"Eur. J. Endocrinol."},{"issue":"1","key":"10.1016\/j.biocel.2026.106987_bib38","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41598-021-04265-w","article-title":"The efficacy of PI3K\u03b3 and EGFR inhibitors on the suppression of the characteristics of cancer stem cells","volume":"12","author":"Xu","year":"2022","journal-title":"Sci. Rep."},{"issue":"4","key":"10.1016\/j.biocel.2026.106987_bib39","first-page":"328","article-title":"Preventing chemotherapy-induced ovarian damage through PI3K\/AKT and Hippo pathway regulation","volume":"33","author":"Zatalian","year":"2025","journal-title":"Support. Care Cancer"},{"issue":"1","key":"10.1016\/j.biocel.2026.106987_bib40","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13048-017-0348-x","article-title":"A retrospective study of reproductive outcomes after fertility-sparing surgery and postoperative adjuvant chemotherapy in malignant ovarian germ cell tumors and sex cord-stromal tumors","volume":"10","author":"Zhang","year":"2017","journal-title":"J. Ovarian Res."},{"issue":"3","key":"10.1016\/j.biocel.2026.106987_bib41","doi-asserted-by":"crossref","first-page":"312","DOI":"10.15283\/ijsc20097","article-title":"The role and specific mechanism of OCT4 in cancer stem cells: a review","volume":"13","author":"Zhang","year":"2020","journal-title":"Int. J. Stem Cells"}],"container-title":["The International Journal of Biochemistry & Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1357272526000919?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1357272526000919?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:56:07Z","timestamp":1786431367000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1357272526000919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":41,"alternative-id":["S1357272526000919"],"URL":"https:\/\/doi.org\/10.1016\/j.biocel.2026.106987","relation":{},"ISSN":["1357-2725"],"issn-type":[{"value":"1357-2725","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting PI3K\u03b3\/AKT1-OCT4\/SOX2 axis with eganelisib suppresses tumor growth and prevents ovarian failure in malignant ovarian germ cell tumors","name":"articletitle","label":"Article Title"},{"value":"The International Journal of Biochemistry & Cell Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biocel.2026.106987","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"106987"}}