Endocrine-related cancer最新文献

{"title":"Management of aggressive PitNETs: evidence gaps, molecular clues, and a roadmap for clinical trials.","authors":"Rafael Loch Batista, Frederic Castinetti, Luciana Ansaneli Naves","doi":"10.1530/ERC-25-0502","DOIUrl":"10.1530/ERC-25-0502","url":null,"abstract":"<p><p>Aggressive and metastatic pituitary neuroendocrine tumors constitute a rare, yet biologically distinct group of lesions, marked by rapid growth, therapeutic resistance, and unpredictable clinical behavior. Despite their rarity, they contribute disproportionately to morbidity due to the absence of reliable prognostic and therapeutic frameworks. Recent evidence has reframed aggressiveness as a multidimensional process shaped by somatic variants, chromosomal instability, and epigenetic remodeling. Recurrent alterations in ATRX, TP53, and SF3B1; widespread copy number losses; and lineage-specific methylation and transcriptomic profiles help delineate tumors with early malignant potential. Single-cell and immune profiling studies reveal proliferative, migratory, and immunoevasive subpopulations that may underpin variable clinical trajectories and treatment responses. Clinically, temozolomide remains the only systemic therapy with consistent benefit, while immune checkpoint inhibitors, anti-VEGF agents, and peptide receptor radionuclide therapy show emerging efficacy in selected settings. Progress will rely on harmonizing diagnostic criteria, integrating molecular and imaging biomarkers, and embedding translational endpoints into clinical trials. Together, these advances define a path toward more precise recognition and management of aggressive pituitary tumors.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687074","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":"Protective TGFβ2/SMAD3 axis identified by TWAS in papillary thyroid cancer.","authors":"Qinnan Zhang, Jiayu Tang, Ju Yang, Yujin Li, Xueqing Li, Kangan Wang, Panpan Zhang, Kai Wang, Bingbing Zha","doi":"10.1530/ERC-25-0405","DOIUrl":"10.1530/ERC-25-0405","url":null,"abstract":"<p><p>Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Although generally indolent, a subset shows aggressive behaviour. Furthermore, the genetic heterogeneity of PTC is not fully explained by known driver mutations, underscoring the need to identify additional susceptibility genes and regulatory mechanisms. To identify additional susceptibility genes and regulatory mechanisms, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomisation (SMR), joint/conditional testing (JCT), and colocalisation analyses across multiple independent cohorts, followed by heterogeneity in dependent instruments (HEIDI) test. Gene prioritisation analyses consistently highlighted TGFB2 and SMAD3 as candidate susceptibility genes for PTC, with SMR supporting putative protective effects. Besides, GEPIA confirmed the positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA. Functional experiments in TPC-1 cells showed that TGFβ2 treatment inhibited cell proliferation and migration, induced apoptosis, and resulted in G0/G1 cell-cycle arrest, accompanied by increased SMAD3 phosphorylation, suggesting activation of canonical TGFβ signalling. Collectively, these findings bridge population-based genetic inference with mechanistic validation and suggest convergent evidence supporting a tumour-suppressive role of the TGFβ2/SMAD3 axis in PTC.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474911","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":"Myeloid landscape of BRAF-mutant papillary thyroid cancer and thyroiditis.","authors":"Sumathy Perampalam, Matti Gild, Adwoa Amoakowa Sey, Lyndal J Tacon, Mitali Fadia, Cathal King, Alexander Papachristos, Mark Sywak, Anthony J Gill, Martyn Bullock, Roderick J Clifton-Bligh","doi":"10.1530/ERC-26-0088","DOIUrl":"10.1530/ERC-26-0088","url":null,"abstract":"<p><p>Papillary thyroid cancer (PTC) is less aggressive when associated with lymphocytic thyroiditis (LT), even in the presence of oncogenic BRAF, including smaller tumours, less lymph node involvement and reduced extrathyroidal extension. To investigate possible immune mechanisms underlying this association, we compared the tumour microenvironment of PTC-BRAF with LT and that without LT using single-cell RNA sequencing (scRNA-seq). Single-cell libraries were generated from fresh and fixed tumour samples with post-dissociation viability >70% using the 10x Genomics Chromium Platform and sequenced on an Illumina NovaSeq 6000. We analysed scRNA-seq data from 11 PTC-BRAF tumours: four with LT (one publicly available sample) and seven without LT. Downstream analyses included quality control, batch correction, dimensionality reduction, and differential gene expression analysis. We found that neutrophils were the predominant myeloid cell type in PTCs without LT. Thyrocytes without LT showed significant expression of the neutrophil recruitment chemokine ECRG4. In the absence of LT, neutrophils expressed oncogenic genes with poor clinical outcomes. In contrast, thyrocytes from tumours with LT showed increased expression of MHC-II antigen presentation, consistent with effective immune surveillance. Thyrocytes and macrophages in the presence of LT showed enrichment of interferon gamma response pathways. Our data suggest that LT in thyroid cancer is associated with enhanced antigen presentation and fewer features of pro-tumourigenic innate immune activity. These results identify previously under-recognised innate immune cell population and associated transcriptomic features, which suggest new mechanisms to target immune treatments in PTC refractory to other therapies.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714957","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":"Single-cell and spatial transcriptomics define a progenitor subpopulation and fibroinflammatory niche at the leading edge of parathyroid carcinoma.","authors":"Ming Cui, Xiang Zhang, Sen Yang, Jinheng Xiao, Qingyuan Zheng, Ou Wang, Xiaoyan Chang, Tianqi Chen, Mengyi Wang, Surong Hua, Ya Hu, Quan Liao","doi":"10.1530/ERC-25-0259","DOIUrl":"10.1530/ERC-25-0259","url":null,"abstract":"<p><p>Parathyroid carcinoma (PC) is a rare but clinically aggressive endocrine malignancy with limited treatment options and a poorly defined tumor microenvironment (TME). To elucidate its cellular heterogeneity and spatial architecture, we integrated single-cell and spatial transcriptomic profiling with whole-exome sequencing and multiplex immunohistochemistry on eight parathyroid neoplasm specimens, including PC, parathyroid adenoma, and atypical parathyroid tumor. We identified a distinct progenitor-like endocrine subpopulation (Ca-1) enriched in CDC73-mutant PC, exhibiting stem-like properties, elevated cell cycle activity, and pronounced genomic instability. Spatial mapping revealed that Ca-1 cells preferentially localize at the leading edge, forming a fibroinflammatory niche characterized by the enrichment of inflammatory cancer-associated fibroblasts (iCAFs) and SPP1+ macrophages. Within this niche, the dipeptidyl peptidase 4 (DPP4) is selectively expressed in Ca-1 cells and iCAFs, implicating a potential paracrine axis driving stromal remodeling and immunosuppression. These findings suggest that a spatially organized ecosystem may promote PC progression through TME remodeling and highlight the DPP4-CXCL2 axis as a candidate pathway for future investigation in aggressive parathyroid neoplasms.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451119","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":"Ageing, parathyroid adenomas and cancer-related outcomes.","authors":"Alanna Silke, Rachel K Crowley","doi":"10.1530/ERC-26-0203","DOIUrl":"10.1530/ERC-26-0203","url":null,"abstract":"<p><p>This narrative review examines the literature on parathyroid disease in the context of ageing, focusing on parathyroid adenoma and parathyroid carcinoma. Parathyroid disease incidence increases with age. We reviewed the available literature on age-related changes in parathyroid physiology and the differences in clinical approach and outcomes in older adults. Available evidence suggests that mechanisms associated with parathyroid adenoma development include structural remodelling of the parathyroid gland, age-related renal function decline and somatic mutations. The evidence for these mechanisms comes from small-scale studies and would benefit from further research. The evidence available suggests that there are some clinical and biochemical differences in parathyroid adenoma presentation in older adults. It also suggests that older adults may be undertreated, with concerns around suitability for surgery driving this. Parathyroid carcinoma has very limited literature available for both its underlying pathophysiology and clinical outcomes. Parathyroid adenoma rarely transforms to parathyroid carcinoma. This literature review shows that ageing does have an impact on the development of parathyroid disease but that there is a lack of large-scale studies around this. We hope this review will help guide further research in this area and, thus, improve care of older adults.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681519","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":"Artificial intelligence in pituitary surgery: the path to clinical solutions.","authors":"George Hudson, Danyal Z Khan, Stephanie E Baldeweg, Hani J Marcus","doi":"10.1530/ERC-26-0104","DOIUrl":"10.1530/ERC-26-0104","url":null,"abstract":"<p><p>Artificial intelligence (AI) is rapidly moving from conceptual innovation to high-performing algorithms across the pituitary patient pathway, promising benefits to patients, endocrinologists and surgeons alike. Pre-operatively, machine learning applied to facial imaging and natural language processing of electronic health records show potential for earlier identification of pituitary adenomas and timelier referral from primary providers to a specialist endocrinologist. Intraoperatively, computer vision systems have already augmented surgical training but have the potential to become integrated real-time decision support systems. Post-operatively, predictive models may help to forecast complications and longer-term remission, endocrinological outcomes or recurrence. Across these domains, the emergence of large, multimodal datasets, which integrate clinical text, endocrinological investigations, radiological imaging, and intraoperative video, promises further AI improvements, yet the impact of AI on real-world clinical decision-making is less clear and depends as much on implementation processes and clinicians themselves. This review provides an overview of AI technologies for pituitary patients and explores some of the challenges translating them to clinical practice.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681600","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":"Characterization of SF3B1 role in prolactin-secreting pituitary tumors.","authors":"Federica Mangili, Anna Maria Barbieri, Genesio Di Muro, Emanuela Esposito, Donatella Treppiedi, Marco Locatelli, Andrea G Lania, Márta Korbonits, Erika Peverelli, Giovanna Mantovani","doi":"10.1530/ERC-25-0527","DOIUrl":"10.1530/ERC-25-0527","url":null,"abstract":"<p><p>Somatic mutations in the gene encoding splicing factor 3B subunit 1 (SF3B1), a key component of the splicing machinery, have been described in patients with PRL-secreting pituitary neuroendocrine tumors (PRL-PitNETs) and associated with aggressiveness and resistance to pharmacological therapy with dopamine agonists (DAs). Dopamine receptor type 2 (DRD2) represents the main target for PRL-PitNET treatment with DAs, even if about 10% of patients is resistant. The aims of the study were to i) test the effects of SF3B1 inhibitor pladienolide B in tumoral lactotroph cells expressing wild-type or mutated SF3B1R625H and ii) investigate the impact of SF3B1 on tumoral cells' responsiveness to DRD2 agonist cabergoline. Pladienolide B treatment reduced cell proliferation (-45.1(15.3)%, P < 0.001) and PRL secretion (-19.25(35.1)%, P < 0.05) and increased apoptosis (+2.4(2.5)-fold, P < 0.05) in rat tumoral MMQ cells. The antimitotic, proapoptotic, and antisecretory effects of pladienolide B were maintained in primary cultured cells from both resistant and responsive PRL-PitNETs. SF3B1R625H overexpression increased tumoral lactotroph proliferation and migration. Moreover, the antimitotic efficacy of pladienolide B, but not of cabergoline, was maintained in MMQ cells transfected with SF3B1R625H. Cabergoline effects on cell proliferation, AKT activation, cyclin D3, and p27 were abolished in MMQ cells silenced for SF3B1. Accordingly, SF3B1R625H overexpression and SF3B1 silencing reduced DRD2 expression at both protein and transcript levels, an effect reverted by nonsense-mediated decay inhibitor NMDI14. In conclusion, we demonstrated a relevant role of SF3B1 in PRL-PitNETs. Indeed, SF3B1 inhibitor pladienolide B exerted antitumoral actions in PRL-PitNET cells bearing wild-type or mutated SF3B1. Moreover, both SF3B1R625H overexpression and SF3B1 genetic silencing reduced DRD2 expression and signaling.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280493","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":"The role of the B7 family in autoimmune thyroid diseases and thyroid cancer.","authors":"Ruidan Zhang, Yulu Che, Yingying Gong, Yixuan Wang, Ziwen Fang, Zongfu Pan","doi":"10.1530/ERC-25-0435","DOIUrl":"10.1530/ERC-25-0435","url":null,"abstract":"<p><p>The B7 family exerts complex and diverse immunomodulatory effects on the occurrence and development of thyroid diseases. The abnormal expression and polymorphisms of B7 family molecules in autoimmune thyroid diseases result in the disruption of immune tolerance, activation of autoreactive T cells, and thyroid tissue damage. The dysfunction of the B7 family is also closely related to the progression of thyroid cancer (TC) through remodeling the tumor microenvironment and mediating immune evasion. Of note, targeting the B7 family has become a promising strategy for TC treatment. In addition, B7 family signaling linking to immune cell subsets, tertiary lymphoid structure formation, and therapeutic response are also discussed. With the emerging findings of B7 family members in thyroid diseases, understanding the comprehensive roles and mechanisms of B7 molecules would facilitate the clinical translation of B7-based immunotherapy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355131","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":"Grade progression and high-grade transformation in neuroendocrine neoplasms.","authors":"Udhayvir S Grewal, Matthew Gosse, Seth J Concors, Raul S Gonzalez, Po Hien Ear, Daniel M Halperin, Chandrikha Chandrasekharan, Simron Singh, Andrew M Bellizzi","doi":"10.1530/ERC-26-0017","DOIUrl":"10.1530/ERC-26-0017","url":null,"abstract":"<p><p>Epithelial neuroendocrine neoplasms (NENs) comprise a biologically diverse group of malignancies that span a wide spectrum of differentiation, proliferative activity, and clinical behavior. Contemporary classifications distinguish well-differentiated neuroendocrine tumors (NETs) from poorly differentiated neuroendocrine carcinomas (NECs). However, growing longitudinal data indicate that a subset of NETs may undergo temporal evolution characterized by rising Ki-67, increasing morphologic atypia, and acquisition of genomic alterations classically associated with NEC, particularly TP53 and, less commonly, RB1 inactivation. These phenomena, referred to as grade progression and high-grade transformation, can result in tumors with NEC-like behavior despite retention of a NET molecular backbone, creating diagnostic and therapeutic ambiguity. In this review, we synthesize recent evidence on the molecular, morphologic, and clinical features of gastroenteropancreatic NET grade progression and transformation, highlight the role of clonal evolution and treatment-associated selection pressure, and discuss implications for imaging, biopsy strategy, molecular profiling, and therapy selection.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431671","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":"Lineage-specific steroidomic signatures in pituitary neuroendocrine tumors: pregnenolone enrichment in SF-1 lineage and associations with tumor behavior.","authors":"Ebubekir Akpinar, Aslihan Pekmezci, Suat Demir, Buruc Erkan, Ebru Turgal, Erdem Altan, Burak Kocak, Huseyin Karatay, Fatih Mert Dogukan, Esra Hatipoglu","doi":"10.1530/ERC-26-0154","DOIUrl":"10.1530/ERC-26-0154","url":null,"abstract":"<p><p>Pituitary neuroendocrine tumors (PitNETs) exhibit diverse biological behaviors, yet the metabolic determinants underlying lineage-specific characteristics remain poorly understood. This study characterized intratumoral steroid metabolite profiles in relation to transcription factor (TF)-defined lineages and radiological tumor features in 69 PitNET specimens obtained during transsphenoidal surgery between 2021 and 2023. Tumors were classified according to the WHO 2022 TF-based criteria (SF-1, PIT-1, and TPIT). Tissue concentrations of 14 steroid metabolites were quantified via liquid chromatography-tandem mass spectrometry, with associations evaluated using multivariable regression and partial least squares discriminant analysis (PLS-DA). Gonadotroph tumors (n = 34) exhibited marked pregnenolone (PREG) elevation compared with other lineages (median: 104.6 vs 1.2 ng/g, P < 0.001, ε2 = 0.38). Corticotroph tumors (n = 9) showed enrichment of glucocorticoid metabolites, particularly 11-deoxycortisol (adjusted P = 0.002, ε2 = 0.30), while PIT-1 tumors (n = 23) displayed intermediate levels. PLS-DA corroborated these patterns, with 11-deoxycortisol and pregnenolone emerging as the primary discriminators (68% total variance). Multivariable analysis confirmed SF-1 lineage to be independently associated with PREG levels after adjusting for clinical and radiological covariates (adjusted R2 = 0.56, P < 0.001). Inverse associations were observed between deoxycorticosterone/11-deoxycortisol and tumor expansion (r = -0.7 and r = -0.4, both P < 0.001), and PREG correlated with cavernous sinus invasion within gonadotroph tumors (P = 0.03). During follow-up (median: 32-38 months), steroid profiles showed no association with clinical outcomes. TF-defined PitNET lineages exhibit distinct intratumoral steroid profiles reflecting intrinsic metabolic properties of lineage-specific cell populations, revealing a novel metabolic dimension to PitNET biology.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304425","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}