Sil Endale Ahanda, Alexandra Lainé, Brunhilde Hanvic, Quentin Verdet, Léa Ikhlef, Antonella De Palma, Sarah Fieuws, Anthony Ferrari, Eric Cumunel, Nicolas Chopin, Christine Rousset-Jablonski, Léa Rossi, Pierre Meeus, Anne-Agathe Serre, Isabelle Treilleux, Isabelle Ray-Coquard, Olivia Le Saux
{"title":"[Understanding biology to identify new therapeutic targets beyond chemotherapy in ovarian granulosa cell tumors].","authors":"Sil Endale Ahanda, Alexandra Lainé, Brunhilde Hanvic, Quentin Verdet, Léa Ikhlef, Antonella De Palma, Sarah Fieuws, Anthony Ferrari, Eric Cumunel, Nicolas Chopin, Christine Rousset-Jablonski, Léa Rossi, Pierre Meeus, Anne-Agathe Serre, Isabelle Treilleux, Isabelle Ray-Coquard, Olivia Le Saux","doi":"10.1016/j.bulcan.2025.07.017","DOIUrl":null,"url":null,"abstract":"<p><p>Granulosa cell tumors (GCTs) are rare ovarian neoplasms, accounting for 2-5% of all ovarian cancers. Two histological types have been described: juvenile (JGCT) and adult (AGCT), the latter accounting for around 95% of the GCTs. AGCTs are mostly diagnosed at an early stage and commonly have a good prognosis. However, GCTs tend to be associated with late recurrence in about a third of cases which are a major concern. These recurrences often require repeated surgical interventions. Systemic treatments, for their part, show limited effectiveness in this context, highlighting the need to identify new therapeutic targets. Thus, better biological characterization of these tumors would enable us to propose more targeted treatments. To achieve this, the molecular characteristics of GCTs have been explored. Most AGCTs harbor a mutation in the FOXL2 transcription factor sequence, therefore allowing to investigate therapeutic perspectives targeting its signalling, as well as setting the first steps towards immunotherapy in these tumors. Knowledge of JGCTs is more limited due to their rarity. However, molecular analysis revealed that ∼60% of the JGCTs bore a genetic mutation in the AKT1 oncogene. However, its clinical significance has still to be explored. For both GCTs subtypes, the CDK4/6-Rb1 axis is promising. Consequently, exploring the molecular features and their role in the biology of these tumors could open up new avenues for targeted and personalized therapies, thereby improving patient care.</p>","PeriodicalId":93917,"journal":{"name":"Bulletin du cancer","volume":" ","pages":""},"PeriodicalIF":0.8000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bulletin du cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.bulcan.2025.07.017","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Granulosa cell tumors (GCTs) are rare ovarian neoplasms, accounting for 2-5% of all ovarian cancers. Two histological types have been described: juvenile (JGCT) and adult (AGCT), the latter accounting for around 95% of the GCTs. AGCTs are mostly diagnosed at an early stage and commonly have a good prognosis. However, GCTs tend to be associated with late recurrence in about a third of cases which are a major concern. These recurrences often require repeated surgical interventions. Systemic treatments, for their part, show limited effectiveness in this context, highlighting the need to identify new therapeutic targets. Thus, better biological characterization of these tumors would enable us to propose more targeted treatments. To achieve this, the molecular characteristics of GCTs have been explored. Most AGCTs harbor a mutation in the FOXL2 transcription factor sequence, therefore allowing to investigate therapeutic perspectives targeting its signalling, as well as setting the first steps towards immunotherapy in these tumors. Knowledge of JGCTs is more limited due to their rarity. However, molecular analysis revealed that ∼60% of the JGCTs bore a genetic mutation in the AKT1 oncogene. However, its clinical significance has still to be explored. For both GCTs subtypes, the CDK4/6-Rb1 axis is promising. Consequently, exploring the molecular features and their role in the biology of these tumors could open up new avenues for targeted and personalized therapies, thereby improving patient care.