Endocrine-related cancer最新文献

{"title":"Familial Mahvash disease with metastatic pancreatic NET and MEN1 mutations.","authors":"Jelka Kuiper, Wouter W de Herder, Yassine Ben Brahim, Marie-Louise F Van Velthuysen, Lodewijk A A Brosens, Richard A Feelders, Janneke G Langendonk, Ronald van Marion, Esther Korpershoek, Gunter Klöppel, Anja Wagner, Johannes Hofland","doi":"10.1530/ERC-25-0087","DOIUrl":"10.1530/ERC-25-0087","url":null,"abstract":"<p><p>Homozygous pathogenic glucagon receptor (GCGR) mutations cause a syndrome with pancreatic glucagon cell hyperplasia and neoplasia (GCHN) and hyperglucagonemia without a glucagonoma syndrome named Mahvash disease. The disease follows an autosomal recessive course and is an exceptionally rare hereditary pancreatic neuroendocrine tumour (panNET) syndrome, with only seven cases documented in the literature. The study aims to elucidate the genotype-phenotype correlation in Mahvash disease and panNET development. Clinical features, molecular profile, pancreatic pathology, and follow-up were studied in detail in six of the 11 family members. The patients' medical records were reviewed up until November 2024. Eight family members were positive for the likely pathogenic GCGR c.455C<T(p.Ser152Phe) germline variant. Three of the family members were homozygous for the GCGR germline variant. Two homozygous patients showed GCHN in pancreatic resection samples, with one of whom exhibiting lymphogenic and hepatic metastases. Three patients each had a glucagon-positive tumour with distinct somatic mutations in the MEN1 gene. One family member, heterozygous for the GCGR variant, presented with three small panNET, with the one biopsied lesion showing glucagon immunoreactivity. We report the first study of a single family with multiple members presenting with GCNH, caused by a novel germline GCGR variant. We are also presenting the first patient with liver metastases in GCHN and another patient with multiple small panNET heterozygous for the novel GCGR gene variant. Our observations highlight the malignant potential for GCHN and suggest that somatic MEN1 mutations may play a role in the development of glucagon-positive panNET from glucagon cell hyperplasia.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM64A contributes to ovarian cancer proliferation and metastasis by suppressing TWIST1 ubiquitination degradation.","authors":"Juan Zhao, Ting Yang, Sijuan Tian, Meili Pei, Minyi Zhao, Li Wang, Xiaofeng Yang","doi":"10.1530/ERC-24-0048","DOIUrl":"10.1530/ERC-24-0048","url":null,"abstract":"<p><p>Ovarian cancer is among the most common cancers among gynecological malignancies. FAM64A is associated with various cancer progressions, but its function and mechanism in ovarian cancer remain unclear. We analyzed and examined the expression of FAM64A in ovarian cancer cells and tissues. The proliferation, migration, and invasion were assessed by knocking down and overexpressing FAM64A in A2780 and SKOV3 cells, respectively. Bioinformatics combined with molecular experiments validated the molecular mechanism of FAM64A. The xenograft tumor model and lung metastasis model were created to explore the impact of FAM64A on tumor growth and metastasis of the nude mice. To evaluate the relative signaling molecule expression, immunohistochemistry (IHC) and Western blot assays were conducted. FAM64A was up-regulated in ovarian cancer tissues and cells and demonstrated to promote the proliferation, migration, and invasion of A2780 and SKOV3 cells in vitro. Bioinformatics and western blot assay indicated that FAM64A could regulate EMT-related transcription factor TWIST1 by suppressing TWIST1 ubiquitination and degradation via the E3 ubiquitin ligase STUB1. Moreover, the Knockdown of FAM64A inhibited tumor growth of xenograft tumor mice and lung metastasis in vivo. FAM64A exerts its oncogene function via regulating TWIST1 ubiquitination and degradation, indicating that FAM64A may provide a promising therapeutic target for the treatment of ovarian cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy of systemic therapies in malignant insulinoma.","authors":"Regina Koch, Patrick Walsh McGarrah, Adrian Vella, Pankaj Shah, Timothy J Hobday, Mohamed Bassam Sonbol, Jason Starr, Rachel Eiring, Travis J McKenzie, Alaa Sada, Patrick Starlinger, Hallbera Gudmundsdottir, Thorvardur R Halfdanarson","doi":"10.1530/ERC-25-0091","DOIUrl":"10.1530/ERC-25-0091","url":null,"abstract":"<p><p>Malignant insulinomas are rare pancreatic neuroendocrine tumors characterized by excessive insulin secretion and a high propensity for metastasis, leading to challenging management. This study retrospectively analyzed 57 patients treated for malignant insulinoma at Mayo Clinic sites between 1992 and 2024, focusing on the efficacy of systemic therapies in improving hypoglycemic control and survival outcomes. The most commonly used therapies included somatostatin analogs (SSA), everolimus, capecitabine-temozolomide (CAPTEM), and peptide receptor radionuclide therapy (PRRT). PRRT demonstrated the highest efficacy in controlling hypoglycemia (93%), followed by CAPTEM (68%) and everolimus (62%). SSA, chemotherapy, and streptozocin were less effective, with hypoglycemic improvement seen in 37.5%, 33.3%, and 28.6% of patients, respectively. Overall survival (OS) was longest with SSA at 84.67 months, followed by CAPTEM at 81.67 months and everolimus at 74.07 months. PRRT demonstrated a median OS of 49.73 months. In contrast, chemotherapy and streptozocin-based therapies had significantly shorter OS times of 15.23 months and 8.35 months, respectively. These findings highlight significant variability in systemic therapy efficacy for malignant insulinoma, with PRRT emerging as a promising treatment for refractory hypoglycemia and long survival. Cox regression analysis identified primary tumor resection and a history of benign insulinoma as associated with longer OS. Optimal sequencing of therapies remains unclear, and individualized treatment plans based on hypoglycemic burden and tumor characteristics are critical for improving survival and quality of life in these patients.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEN2: surgical precision in the era of precision medicine.","authors":"Tom R Kurzawinski, Colin R Butler, Tarek Abdel Aziz","doi":"10.1530/ERC-24-0251","DOIUrl":"https://doi.org/10.1530/ERC-24-0251","url":null,"abstract":"<p><p>Medullary Thyroid Cancer, Phaeochromocytoma and Primary Hyperparathyroidism in patients with Multiple Endocrine Neoplasia type 2 can all be cured by surgery on the condition that they are detected early, before locoregional or distant spread of malignant disease occurs and long term metabolic and structural damage to cardiovascular, renal, skeletal systems takes place. Recent scientific discoveries and technological advances made surgical decision process more precise and facilitated personalised treatments. RET analysis enables us to see this syndrome not as a monolith but as a cluster of different phenotypic presentations, each sending patient on an individual journey, which can be anticipated but not determined. Biochemical monitoring provides regular updates on transformation of endocrine cells in target endocrine organs, and together with imaging, helps to decide on time and extend of surgery. Advances in surgical technology allows for safer and less invasive interventions resulting in fewer complications, less trauma and better functional outcomes. Calibrating magnitude of surgery able to cure but do minimal harm, timing and performing it well is the art of the surgical precision in MEN2 patients. Surgical outcomes have improved in the last 30 years and we need to continue on this road. Precision in surgery aiming at near perfect surgical performance is achievable, and this mini review looks at surgical decision making process through the prism of genetics and biochemical testing combined with imaging, former setting a trajectory for the disease progression with a fair degree of probability, and latter assessing functional and structural changes over time.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome sequencing reveals distinct atypical parathyroid tumor subtypes.","authors":"Hye-Sun Park, Milim Kim, Se-Young Jo, Gi Jeong Kim, Jong Ju Jeong, Namki Hong, Sangwoo Kim, Yumie Rhee","doi":"10.1530/ERC-25-0057","DOIUrl":"https://doi.org/10.1530/ERC-25-0057","url":null,"abstract":"<p><p>Atypical parathyroid tumors (APTs) are a rare subtype of parathyroid neoplasms characterized by diagnostic challenges and an uncertain prognosis. This study aimed to validate the subtypes of APTs using transcriptome sequencing. We applied a clustering model developed for our previous study, in which we had successfully distinguished parathyroid cancer from adenomas using gene expression patterns. Sixteen patients with APT who had undergone parathyroidectomy were enrolled, and we analyzed their baseline data, pathologic reports, and follow-up records and performed transcriptome sequencing of their APT samples. We then used our clustering model to classify tumors as either cancer- or adenoma-type APTs and compared these results with clinical findings. The median age of patients was 48.9 years, with median calcium and parathyroid hormone (PTH) levels of 11.4 mg/dL and 420.0 pg/mL, respectively. Pathologic and immunohistochemical results did not reveal any remarkable differences between adenoma-type and cancer-type APTs. However, clustering analysis classified four of the 16 APTs as being cancer-type and 12 as being adenoma-type tumors. Cancer-type patients had a median age of 30.0 years, with median calcium and PTH levels of 12.6 mg/dL and 800.8 pg/mL, respectively, clinically resembling parathyroid cancer. One patient exhibited a somatic CDC73 two-hit mutation and positive WT1 staining, suggesting a high malignant potential. Clustering analysis through transcriptome sequencing shows promise for risk stratification of patients with APTs. For those classified as having cancer-type tumors, close monitoring and long-term follow-up may be warranted.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy-related myeloid neoplasms in 177Lu-DOTATATE treated neuroendocrine tumor patients: how great is the risk?","authors":"Yael Kusne, Mrinal M Patnaik, Thorvardur R Halfdanarson, Mohamad Bassam Sonbol","doi":"10.1530/ERC-25-0025","DOIUrl":"https://doi.org/10.1530/ERC-25-0025","url":null,"abstract":"<p><p>Peptide receptor radionuclide therapy (PRRT) with lutetium-177-Dotatate (177Lu-DOTATATE) has transformed neuroendocrine tumor (NET) treatment, improving progression-free survival, symptom control, and quality of life. However, long-term hematologic toxicities, including therapy-related myeloid neoplasms (tMN), are increasingly recognized. These rare but severe complications, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), appear multifactorial, influenced by prior cytotoxic therapies, radiation exposure, clonal hematopoiesis, and germline predispositions. This review synthesizes data on PRRT-related hematologic toxicities, including findings from pivotal studies and real-world evidence. We explore risk factors, underlying mechanisms, and the potential role of biomarkers such as clonal hematopoiesis and germline mutations in predicting toxicity. Emerging approaches, including alpha particle radioligand therapy and advanced dosimetry are explored as strategies to optimize patient selection and minimize adverse outcomes. To maximize the benefits of PRRT while safeguarding patient safety, future efforts should focus on integrating predictive biomarkers, refining treatment sequencing, and developing personalized, risk-stratified approaches to therapy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-specific neoplastic risk profiles in patients with VHL disease.","authors":"Athina Ganner, Alfonso Massimiliano Ferrara, Peggy Sekula, Francesca Schiavi, Julia H Joo, Gabriela Sanso, Madson Q Almeida, Anna Laura Knoblauch, Christine Julia Gizaw, Karol Krzystolik, Sophie Charlotte Astheimer, Maria Isabel Achatz, Ana Vieites, Diane Donegan, Thomas Hundsberger, Jan Lubinski, Ilgin Yildirim Simsir, Tushar Bandgar, Kornelia Hasse-Lazar, Agnieszka Pawlaczek, Wouter Zandee, Kai Yu, Claudio E Kater, Liliya Rostomyan, Xiao-Ping Qi, Timo Deutschbein, Hanna Remde, Tabatha Nakakogue Dallagnol, Marina Yukina, Rene Baudrand, Corina E Andreescu, Tada Kunavisarut, Nur Diana Ishak, Xavier Le Guillou Horn, Gemma Shutler, Milan Jovanovic, Mariola Pęczkowska, Jan Calissendorff, Francesco Circosta, Maria João Bugalho, Eleonora P M Corssmit, Oliver Gimm, Marcus Quinkler, Andrea Goldmann, Sara Watutantrige Fernando, Stefania Zovato, Lucas S Santana, Felipe Freitas-Castro, Christian Rothermundt, Josa Zimmermann, Asude Durmaz, Ayca Aykut, Laurent Vroonen, Tobias Krauss, Christian Taschner, Juri Ruf, Jan-Helge Klingler, Sven Gläsker, Stefan Lang, Felicitas Bucher, Hansjürgen Agostini, Cordula Jilg, Wolfgang Schultze-Seemann, Birke Bausch, Antonia Bergfeld, Kilian Rhein, Thomas Uslar, Antonio Concistrè, C Christofer Juhlin, José Cláudio Casali-da-Rocha, Luigi Petramala, Uliana Tsoy, Elena Grineva, Xu-Dong Fang, Fruzsina Kotsis, Tobias Schaefer, Thera P Links, Özer Makay, Gustavo F C Fagundes, Joanne Ngeow, Nalini Shah, Giuseppe Opocher, Marta Barontini, Catharina Larsson, Andrzej Januszewicz, José Viana Lima, Nelson Wohllk, Claudio Letizia, Gianluca Donatini, Eamonn R Maher, Dmitry Beltsevich, Irina Bancos, Cezary Cybulski, Martin K Walz, Anna Köttgen, Charis Eng, Hartmut P H Neumann, Elke Neumann-Haefelin","doi":"10.1530/ERC-24-0260","DOIUrl":"10.1530/ERC-24-0260","url":null,"abstract":"<p><p>Hereditary tumor predisposition syndromes pose a challenge for early detection and timely treatment of tumors. In von Hippel-Lindau disease, desirable personalized surveillance programs are lacking due to insufficient data on genotype-specific risk profiles of individual mutations. To describe neoplastic risk profiles for carriers of pathogenic and likely pathogenic VHL germline mutations, our observational study recruited 1,350 participants from 40 centers worldwide. 432 different VHL germline mutations were observed, with p.Asn78Ser, p.Arg161Ter, p.Arg161Gln, p.Arg167Gln, p.Arg167Trp and p.Tyr98His being the six most frequent, occurring in a total of 493 carriers (36.5%) and in ≥30 patients each. Age-related penetrance risks for retinal hemangioblastoma, central nervous system hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumors and pheochromocytoma/paraganglioma in carriers of the most frequent VHL mutations were assessed. In addition, the number of organs affected, the frequency of surgery and the outcome are reported. Pairwise comparisons of the age-dependent tumor penetrance of these six mutations showed that 47 out of 90 pairs were significantly different. The most significant associations were found in p.Tyr98His (n = 19), followed by p.Arg161Ter (n = 10). All pairwise comparisons of mutations affecting different codons showed at least one significant (P < 0.05) difference, except for p.Asn78Ser vs p.Arg161Ter. Thus, tumor risk varied by VHL mutation type and location, but did not differ between the truncating mutation p.Arg161Ter and the missense mutation p.Asn78Ser. Our study demonstrates the importance of mutation-specific phenotype prediction. With appropriate validation, the data have important implications for risk assessment and decision making in tumor prevention for carriers of the respective VHL mutations.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spanish consensus on the diagnosis and management of adrenocortical carcinoma.","authors":"Marta Araujo-Castro, Cristina Álvarez-Escola, Ana Casteràs, Alberto Carmona-Bayonas, María-Dolores Chiara, Felicia A Hanzu, Jorge Hernando, José L Vercher-Conejero, Macarena Rodríguez-Fraile, Victoria Gómez Dos Santos, Paula Jimenez-Fonseca, Alexandra Giraldo, Nuria Valdés, Oscar Vidal, Maribel Del Olmo-García, Jaume Capdevila","doi":"10.1530/ERC-25-0034","DOIUrl":"https://doi.org/10.1530/ERC-25-0034","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an estimated incidence of 0.7-2 cases per million/year. The rarity of this disease, coupled with limited preclinical models and clinical trials, has hindered progress, resulting in poor outcomes, with a 5-year survival rate of approximately 35%. Currently, the only available curative treatment is complete surgical resection of the adrenal tumor. For unresectable or metastatic ACC, the current standard therapeutic modalities are mitotane, chemotherapy, radiotherapy and locoregional treatments; however, these are noncurative. Mitotane has an adrenolytic and anti-steroidogenic effect, and it is used in the adjuvant setting for high-risk patients, as systemic therapy for metastatic disease, and/or to control hormonal secretion. While key pathways in ACC pathogenesis have been identified as potential therapeutic targets, results with targeted therapies remain modest, showing that there is a clinical unmet need for novel treatments or new combinations of exiting drugs. Effective management requires a multidisciplinary team of experts to optimize outcomes for patients. This article presents a multidisciplinary consensus on the diagnosis, management, prognosis and follow-up of patients with ACC, and the approach to two special contexts, ACC in pregnant women and hormone-producing ACC. The consensus was coordinated by the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Group of Neuroendocrine and Endocrine Tumors (GETNE), with contribution from experts from related societies including the Spanish Association of Surgeons (AEC), Spanish Society of Urology (AEU), Anatomic-Pathology (SEAP), Nuclear Medicine (SEMNIM), Medical Oncology (SEOM) and Radiotherapeutic Oncology (SEOR).</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From bench to bedside in the sella: translational developments in pituitary tumour genetics.","authors":"Sunita M C De Sousa","doi":"10.1530/ERC-24-0272","DOIUrl":"10.1530/ERC-24-0272","url":null,"abstract":"<p><p>The two most prevalent pituitary tumour types are pituitary adenomas (also referred to as pituitary neuroendocrine tumours or pitNETs) and craniopharyngiomas, collectively accounting for 98% of all pituitary tumours. The genetic basis of these pituitary tumours is partly understood. In pituitary adenomas, established predisposition genes in the germline setting are MEN1, PRKAR1A, AIP, CDKN1B, GPR101 and the SDHx genes, while somatic driver mutations are well described in GNAS in somatotrophinomas and in USP8 in corticotrophinomas. Craniopharyngiomas are not heritable tumours, but there is a clear genetic basis at the somatic level, with clonal CTNNB1 and BRAF variants present in approximately 95% of adamantinomatous and papillary craniopharyngiomas, respectively. This review explores mechanistic developments in these established genes, new genes in the pituitary adenoma setting (e.g. MAX, CABLES1, CDH23, PAM or CHEK2), and emerging uses of CTNNB1/BRAF testing in the craniopharyngioma setting. It concludes with a discussion of the bench-to-bedside translations of these scientific discoveries as they pertain to clinicians seeing patients with these sellar tumours. In current clinical practice, the most readily applicable and directly impactful translations of recent pituitary genetic research are the opportunities for germline DNA testing for familial pituitary tumour syndromes and tumour DNA testing of craniopharyngiomas to confirm diagnosis (adamantinomatous/papillary craniopharyngioma) and guide treatment (in papillary craniopharyngioma).</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual dimorphism in thyroid cancer: evidence from preclinical studies.","authors":"Francesca Coperchini, Alessia Greco, Paolo Caccavale, Isabella Chiardi, Laura Croce, Marsida Teliti, Flavia Magri, Mario Rotondi","doi":"10.1530/ERC-24-0348","DOIUrl":"10.1530/ERC-24-0348","url":null,"abstract":"<p><p>Thyroid cancer (TC) exhibits strong sexual dimorphism, with higher incidence rates observed in females and more aggressive behavior in males. This disparity arises from complex interactions among genetic, hormonal and environmental factors. Data from preclinical studies evidenced a crucial role of sex hormones in driving TC prevalence and/or progression in males and females. In particular, estrogens would play a pro-tumorigenic role by directly activating estrogen receptor pathways and indirectly influencing tumorigenesis through mechanisms such as oxidative stress modulation, stimulation of thyroid stem cell proliferation, and alterations in the tumor microenvironment. Instead, androgens and androgen receptor (AR) signaling would exhibit dual roles in TC. AR downregulation in thyroid tissues is associated with increased tumor progression, whereas AR overexpression has demonstrated protective effects. These include inhibition of epithelial-to-mesenchymal transition, suppression of cell proliferation, downregulation of PD-L1 expression, and suppression of oncogenic microRNAs such as miR-146b. Conversely, androgens can promote tumor aggressiveness and metastasis in certain contexts, such as through VEGFC/VEGFR-3 signaling when a specific androgen-regulated gene is overexpressed. This review is aimed at summarizing the recent evidence coming from the literature data regarding both in vitro and in vivo studies on animal models investigating the multifaceted roles of sex hormones in TC, highlighting the critical need for new prospective longitudinal studies, also in view of gender-affirming hormones therapy. Such research will enhance our understanding of hormonal influences across diverse populations and further explain the relationship between sexual dimorphism and TC pathogenesis.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}