{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:45:43Z","timestamp":1782456343511,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adult granulosa cell tumor (aGCT) is a rare ovarian malignancy with frequent late recurrences and limited systemic treatment options. Emerging evidence suggests that dysregulation of the cyclin D\u2013cyclin-dependent kinase (CDK) 4\/6\u2013retinoblastoma (Rb) axis contributes to aGCT biology, while hormone receptor expression supports the potential role of endocrine therapy. We performed a scoping review to map available evidence on CDK4\/6 inhibition in aGCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A literature search was conducted in PubMed\/MEDLINE, Embase and Web of Science, complemented by searches of trial registries, conference abstracts and citation searching. Eligible reports included translational, preclinical and clinical studies addressing CDK4\/6 pathway dysregulation or CDK4\/6 inhibition in aGCT. Evidence on endocrine therapy was synthesized narratively to contextualize combination strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-three reports were included. Translational and genomic studies showed recurrent abnormalities affecting cell-cycle regulation, including alterations in CDK inhibitors, Rb-associated signaling and other proliferation-related pathways. Preclinical studies demonstrated that CDK4\/6 inhibition, particularly with abemaciclib, reduced cell viability and tumor growth in GCT models. Clinical evidence was limited to small retrospective case series, which suggested clinically meaningful disease control in a subset of patients with recurrent disease. An ongoing phase II trial is expected to provide the first systematic evaluation of this therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Available evidence supports CDK4\/6 inhibition as a biologically plausible therapeutic strategy in aGCT. Although current clinical data remain limited, the combination of CDK4\/6 inhibitors with endocrine therapy appears promising and warrants prospective evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1844395","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:46:07Z","timestamp":1782452767000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cyclin-dependent kinase 4\/6 inhibitors in granulosa cell tumors and their combination with hormonal therapy: a scoping review"],"prefix":"10.3389","volume":"16","author":[{"given":"Renata","family":"Pacholczak-Madej","sequence":"first","affiliation":[{"name":"Department of Gynecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology","place":["Krakow, Poland"]},{"name":"Department of Anatomy, Jagiellonian University, Medical College","place":["Krakow, 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