Endocrine-related cancer最新文献

{"title":"DLK1: a novel therapeutic target in cancer.","authors":"James Frederick Henry Pittaway","doi":"10.1530/ERC-25-0513","DOIUrl":"10.1530/ERC-25-0513","url":null,"abstract":"<p><strong>Abstract: </strong>Delta-like non-canonical Notch ligand 1 (DLK1) is a cleavable transmembrane protein with tightly regulated, developmentally restricted expression. It is highly expressed during embryogenesis, where it plays a key role in controlling cellular differentiation and proliferation, but is largely silenced in adult tissues, persisting mainly within stem and progenitor compartments of endocrine organs. Notably, DLK1 is consistently re-expressed across a broad range of malignancies, with the highest prevalence observed in endocrine and neuroendocrine tumours, including adrenocortical carcinoma, phaeochromocytoma/paraganglioma, medullary thyroid carcinoma, and neuroblastoma. DLK1 expression is associated with adverse clinical outcomes and is increasingly implicated in maintaining a de-differentiated, stem-like tumour phenotype that might contribute to tumour progression and therapeutic resistance. The restricted expression of DLK1 in normal adult tissues, combined with its cell-surface localisation and functional relevance in tumour biology, makes it an attractive therapeutic target, particularly in endocrine malignancies where targetable options remain limited. Multiple DLK1-directed strategies are now advancing through preclinical and early clinical development, including afucosylated monoclonal antibodies, antibody-drug conjugates, dendritic cell vaccines, chimeric antigen receptor T-cell therapies, and radioimmunotherapy. Early-phase studies demonstrate encouraging safety profiles and signals of efficacy, with emerging evidence suggesting that tumour-specific factors - such as steroidogenesis, immune microenvironment, and drug efflux mechanisms - may influence response in endocrine cancers. This review collates current evidence on DLK1 biology and therapeutic targeting, with a focus on endocrine and neuroendocrine malignancies. We highlight key novel mechanistic insights, translational challenges, and future opportunities to exploit DLK1 as a precision therapeutic target in these high-need cancer subtypes.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792779","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":"Updating ACC preclinical models: characterization of two new patient-derived cell lines.","authors":"Andrea Abate, Mariangela Tamburello, Claudia Bonera, Guido Alberto Massimo Tiberio, Sara Baldelli, Mattia Carini, Alessia Inglesi, Maria Scatolini, Deborah Cosentini, Marta Laganà, Marta Leporati, Pietro Luigi Poliani, Domenico Cosseddu, Duilio Brugnoni, Alfredo Berruti, Sandra Sigala","doi":"10.1530/ERC-25-0317","DOIUrl":"10.1530/ERC-25-0317","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is an aggressive, rare and heterogeneous malignancy that requires diverse preclinical models. For this reason, the development of new cell lines is pivotal. This article describes the development and characterization of two of them, SMAC-2 and SMAC-3, established from surgical specimens of ACC patients. The characterization included their mutational profiling, the evaluation of the expression of steroidogenic enzymes, secretory activity and the expression of steroid hormone receptors. The proliferative ability of these cells within zebrafish embryo xenografts was also evaluated. SMAC-2 originated from a metastatic EDP-M-treated ACC in a female patient with hypercortisolism and hyperandrogenism, while SMAC-3 derived from a male patient with a mitotane-treated local recurrence, with no sign of hypercortisolism. TP53 was mutated in both lines. SMAC-2 cells were characterized by a pathogenic alteration on CTTNB1 gene and a deletion of CDKN2A gene, while SMAC-3 on MSH2 gene. Basal hormonal status analysis showed a cell model-specific fingerprint either in the hormonal secretion or in the gene and protein expression of steroid hormone receptors. SMAC-2 secreted high levels of cortisol. SMAC-3 secreted low basal levels of cortisol. Mitotane displayed a low potency in both cell lines. Under the experimental conditions used, the xenografted area did not increase in both cell models. Experiments were carried out to study the stability of the two cell lines. SMAC-2 and SMAC-3 display unique molecular and functional features, expanding the repertoire of experimental ACC models and representing valuable tools for preclinical research alongside established cell lines.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876760","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":"Convergent IGF2 overexpression in pheochromocytoma/paraganglioma: insights from Beckwith-Wiedemann syndrome.","authors":"Hussam Alkaissi, Christopher A Febres-Aldana, Sara Talvacchio, Herui Wang, Catherine M Gordon, Karel Pacak","doi":"10.1530/ERC-26-0061","DOIUrl":"10.1530/ERC-26-0061","url":null,"abstract":"<p><p>Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth and tumor predisposition, caused by dysregulated expression of genes on chromosome 11p15.5. An association between BWS and pheochromocytoma/paraganglioma (PPGL) has been suggested in isolated case reports over the past fifty years, but the molecular basis for this link remains unclear. We identified four patients with BWS who developed metastatic PPGL and investigated IGF2 pathway activation in these tumors and in PPGL across various genotypes. Pan-cancer transcriptomic analysis of The Cancer Genome Atlas (TCGA) demonstrated that PPGL overexpresses IGF2, with pseudohypoxic tumors exhibiting higher expression compared to other molecular clusters. Loss of heterozygosity and loss of imprinting at 11p15.5 partially explain this overexpression, with PPGL additionally demonstrating globally elevated expression of imprinted genes compared to most other tumor types, suggesting a broader relaxation of genomic imprinting. Cognate receptor profiling revealed that PPGLs are equipped to respond to IGF2 signaling, with high expression of IGF1R and insulin receptor isoform A (IR-A). Immunohistochemistry confirmed IGF2 protein overexpression in both BWS-associated and genotypically diverse sporadic PPGLs. Our results indicate that IGF2 overexpression is a convergent molecular feature of PPGL across genotypes and suggest the IGF2 pathway as a potential diagnostic and therapeutic target.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876801","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":"Unravelling mesenteric fibrosis in small intestinal neuroendocrine tumours and implications for clinical management.","authors":"Maria Castanho Martins, Eva van der Slik, Johannes Hofland, Anela Blažević, Harry Hodgetts, Dalvinder Mandair, Christos Toumpanakis, Martyn E Caplin, Leo J Hofland, Wouter W de Herder, Krista Rombouts, Richard A Feelders","doi":"10.1530/ERC-25-0116","DOIUrl":"10.1530/ERC-25-0116","url":null,"abstract":"<p><p>Mesenteric fibrosis (MF) is an extensive fibrotic reaction common in small intestine neuroendocrine tumours (SI-NETs) and develops around mesenteric metastasis. While primary SI-NETs can remain asymptomatic for years, mesenteric metastasis (MM) and the resulting MF frequently leads to serious complications. Despite its clear impact on quality of life, MF pathophysiology remains poorly understood and treatment options are currently limited to surgical interventions. This review summarizes the literature on MF in SI-NET patients, emphasizing gaps in knowledge and potential research directions. Clinical research confirms that MF is a frequent complication, often causing severe morbidity, including mesenteric ischaemia and obstruction. Addressing these issues requires further research into MF pathogenesis and contributory factors, such as elastic vascular sclerosis (EVS), which are currently underexplored. Advancing this field will necessitate collaboration, supported by clear definitions and standardized diagnostic and grading systems for MF linked to clinical data, which are presently lacking. While MF-directed translational research remains scarce, recent studies focusing on tumour microenvironment have begun to uncover possible pathways involved in MF. Serotonin, pro-fibrotic growth factors and cytokines may play a role in activating cancer-associated fibroblasts and immune cells within the tumour microenvironment, aggravating extracellular matrix protein deposition and possibly creating positive feedback loops that promote fibrosis. Recently classified as an organ, the mesentery may harbour unique properties for stimulating the establishment of MF. Emerging research is paving the way for new MF treatment options that are urgently needed.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731014","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":"Proteomic signatures of adipocyte recruitment in breast cancer.","authors":"Dimitrios G Argyris, Ioanna Ploumaki, Theodora Argyri, Dimitra P Anastasiadou, Nikos S Karagiannis, Maria P Pavlou, Evanthia T Roussos Torres, Outhiriaradjou Benard, Rachel B Hazan, Panagiota S Filippou, George S Karagiannis","doi":"10.1530/ERC-25-0361","DOIUrl":"10.1530/ERC-25-0361","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is increasingly recognized as a dynamic regulator of breast cancer progression, with adipocytes functioning as active contributors rather than passive bystanders. Here, we investigated the proteomic and morphologic reprogramming of breast cancer-associated adipocytes (BrCAAs) in response to triple-negative breast cancer (TNBC). Using conditioned medium from HCC1143 cells, we established an in vitro BrCAA model and performed mass spectrometry-based proteomics. Comparative profiling revealed 256 differentially expressed proteins, enriched for pathways including fatty acid degradation, carbon metabolism, and glycogen turnover, consistent with a metabolic shift from energy storage to energy supply. Gene ontology and protein-protein interaction analyses further identified cytoskeletal remodeling, adhesion dynamics, and secretory pathway activation, supporting BrCAA-driven microenvironmental remodeling. In the MMTV-PyMT mouse model, morphometric analysis demonstrated progressive size reduction and increased contour irregularity of adipocytes adjacent to tumors, correlating with proteomic evidence of metabolic stress. Importantly, BrCAAs localized at tumor interfaces were associated with increased microvessel density and CD105+ endothelial activation compared to desmoplastic zones. Proteomic enrichment highlighted pro-angiogenic remodeling, with validation of basigin (BSG), integrin αV (ITGAV), and 2,4-dienoyl-CoA reductase 1 (DECR1). Collectively, our findings establish BrCAAs as metabolically and structurally reprogrammed stromal components that promote tumor metabolism and localized angiogenesis, representing potential therapeutic targets in aggressive breast cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655600","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":"Determinants of false-positive plasma free metanephrines and methoxytyramine: the role of medications and chronic disease.","authors":"Lara M Knigge, Kristin Potthoff, Georgiana Constantinescu, Sybille Fuld, Karolina Zawadzka, Ermal Tahirukaj, Stefan Bornstein, Jacques W M Lenders, Graeme Eisenhofer, Christina Pamporaki","doi":"10.1530/ERC-25-0549","DOIUrl":"10.1530/ERC-25-0549","url":null,"abstract":"<p><p>Measurements of plasma free metanephrines provide a highly sensitive test for the diagnosis of pheochromocytoma/paraganglioma (PPGL). However, false-positive results remain common, posing a diagnostic dilemma for clinicians. The aim of this study was to determine whether chronic illness and commonly prescribed drugs can falsely elevate plasma free metanephrines. This retrospective study included 460 patients without PPGL. Disease exclusion was based on negative imaging or histopathological findings, or negative biochemistry at follow-up. Sex, age, plasma free normetanephrine, metanephrine, and methoxytyramine, the presence or absence of cardiometabolic comorbidities and/or chronic illness (CCI), and all prescribed medications at study inclusion were reported. In four patients under treatment with norepinephrine reuptake blockers (NRBs), metanephrines were measured at baseline and after short-term discontinuation of the drug. Among the 460 patients without PPGL, 88% (407/460) were receiving at least one medication. In this cohort, false-positive elevations of plasma free metanephrines were rare (7%). Multivariable analysis identified NRBs as the only drugs independently associated with increased plasma free normetanephrine levels (P < 0.001), in a dose-dependent manner. Importantly, plasma free methoxytyramine concentrations were independently influenced by NRBs, antipsychotics, and nicotine use (P < 0.001). Paired analyses in a subset of four patients before and after short-term NRB withdrawal showed normalization of plasma free normetanephrine concentrations. Plasma free metanephrines show high diagnostic reliability with minimal interference from CCI or commonly used medications. However, NRBs can increase normetanephrine and methoxytyramine concentrations, particularly at higher doses, and thus, their use requires cautious interpretation of plasma free metanephrine measurements.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730961","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":"NP-101 in combination with nivolumab and ipilimumab in metastatic extrapulmonary neuroendocrine carcinomas (EP-NECs): A pilot study.","authors":"A Mohamed, A Azmi, M Kocak, M B Sonbol, B Konda, A Dowlati, C Nagel, M Haider, B Laderian, S L Asa, S H Tirumani, J Garcia, A Mahipal, D Bajor, S Chakrabarti, J E Selfridge, M Conces, M Lumish, R S Hoehn, J Winter, P Fu, J Ammori, J Hardacre, L E Henke, H Y Khan, C Morgan, D Abedal Raheem, D Donohue, P Fowler, A Kaseb","doi":"10.1530/ERC-25-0232","DOIUrl":"10.1530/ERC-25-0232","url":null,"abstract":"<p><p>Extrapulmonary neuroendocrine carcinomas (EP-NECs) are a heterogeneous group of rare tumors with poor clinical outcomes. These patients have limited treatment options after progressing on first-line platinum-based chemotherapy. Although dual immune checkpoint inhibitors (ICIs) with anti-CTLA-4 and anti-PD-1 blockade have significantly improved outcomes for several solid tumors, they demonstrated modest activity for EP-NECs with 9-26% response rates and low survival rates. Preliminary data demonstrated that NP-101 (Nigella sativa formulation) enhances T-cell infiltration and is synergistic with dual ICPIs in NECs' cellular models. This pilot study evaluated the tolerability and efficacy of NP-101 plus nivolumab and ipilimumab in patients with metastatic EP-NECs refractory to first-line platinum-based chemotherapy. This is a single-arm pilot study (NCTNCT05262556) in which patients with metastatic EP-NECs received NP-101 (oral capsules), 3,000 mg daily, plus ICPIs (intravenous nivolumab 3 mg/kg and ipilimumab 1 mg/kg) every 3 weeks for four cycles. Nonprogressors received NP-101 (3,000 mg daily), plus biweekly maintenance of nivolumab (240 mg), and then completed 24 weeks of treatment. Treatment-related adverse events (TR-AEs) were characterized according to CTCAE v4.03. The response rate was estimated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The Kaplan-Meir method was used to estimate median PFS and OS. Twelve patients received ≥1 dose of NP-101 and nivolumab plus ipilimumab. There were no dose-limiting toxicities (DLTs). Grade 1/2 TR-AEs occurred in 100% (12/12) of patients. The most common G1/2 TR-AEs included the following: fatigue (75%), nausea (41.7%), pruritus (41.7%), muscle weakness (33.3%), vomiting (25%), rash (25%), and abdominal pain (25%). Eight patients (66%) experienced grade 3/4 TR-AEs, including rash (33.3%), nausea (16.7%), vomiting (16.7%), and transaminitis (16.7%). No treatment-related grade 5 toxicities or deaths were recorded. The objective response rate was 41.7% (2/12 (16%) complete response (CR) + 3/12 (25%) partial response (PR); 95% CI: 15.2-72.3%) for all patients and 50% (2/8 CR + 2/8 PR, 95% CI: 0.16-0.84) for patients with NEC of gastrointestinal origin. The median duration of response was 7.5 months. As for the median progression-free survival, it was 5.7 months, and the median overall survival (OS) was 10.5 months with a median follow-up of 10.4 months. The combination of NP-101 plus dual ICPIs (nivolumab and ipilimumab) was safe and well tolerated with preliminary evidence of antineoplastic activity. Currently, a randomized phase II clinical trial evaluating the combination is under development.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792804","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":"Phaeochromocytomas and paragangliomas harbour tumour-initiating SOX2+ stem cells.","authors":"Yasmine Kemkem, Mark Quinn, Bence Kövér, Alice Santambrogio, James Kaufman-Cook, Olivia Sherwin, Laura D Scriba, Dimitria Brempou, Miriam Vazquez Segoviano, Dylan Cameron, Ilona Berger, Wen Ng, Daisuke Nonaka, Marily Theodoropoulou, Christina Pamporaki, Paul V Carroll, Louise Izatt, J Paul Chapple, Stefan R Bornstein, Nicole Bechmann, Charlotte Steenblock, Rebecca J Oakey, Cynthia L Andoniadou","doi":"10.1530/ERC-25-0242","DOIUrl":"10.1530/ERC-25-0242","url":null,"abstract":"<p><p>Phaeochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumours that arise in the neural crest (NC)-derived adrenal medulla and the paraganglia, respectively. Approximately 10-15% of patients with PCCs and 35-40% with PGLs go on to develop metastatic disease, leading to a reported median overall survival of 7 years. The development of prognostic markers and subsequent personal therapeutic strategies are hindered by a lack of understanding of tumourigenesis. In other organs, cells with stem-like properties are at the root of tumour initiation and maintenance, due to their ability to self-renew and give rise to differentiated cells. We have recently shown that, in the human adrenal, a subset of sustentacular cells, endowed with a support role, are in fact SOX2+ postnatal adrenomedullary stem cells that are specified along the NC migratory route. In this study, we intended to determine if SOX2+ cells in PCCs and PGLs can behave as tumour-initiating stem cells. Using expression and transcriptomic studies, we demonstrate the presence of SOX2/SOX2-expressing cells across a broad range of PCCs and PGLs, irrespective of tumour aggressiveness, location, and causative mutation. In silico analyses reveal the co-expression of SOX2 and chromaffin cell markers in the tumour and reveal the active proliferation of these double-positive cells. Isolation of these cells in vitro in stem cell-promoting media, and their xenotransplantation on chicken chorioallantoic membranes, demonstrates that they have the potential to expand and metastasise in ovo, supporting their potential as tumour-initiating cells.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792785","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":"Systematic review of the molecular basis for cavernous sinus invasion in somatotropinomas.","authors":"Christopher Dillon Ovenden, Nicholas Candy, Stephen Bacchi, Alexandra Sorvina, Mendel Castle-Kirszbaum, Santosh Poonnoose, Nikitas Vrodos, Alistair Jukes, Stephen Santoreneos, David J Torpy, Alkis Psaltis, Sunita De Sousa","doi":"10.1530/ERC-25-0236","DOIUrl":"10.1530/ERC-25-0236","url":null,"abstract":"<p><p>Somatotropinomas are a subtype of pituitary adenomas that have a particular predilection to invade the cavernous sinus. The objective of this systematic review was to examine the evidence regarding the molecular basis for cavernous sinus invasion in somatotropinomas. This review was conducted in accordance with the 2020 PRISMA guidelines on 13 April 2025. Inclusion criteria were reports of associations between somatotropinoma molecular changes and cavernous sinus invasion in adult patients. Title/abstract screening and full-text screening were performed, with studies assessed for risk of bias using the Newcastle-Ottawa scale. A total of 43 studies were identified, encompassing 1,824 patients (724 invasive tumours). Overall, 33 studies identified molecules that were upregulated in invasive tumours and 20 studies identified molecules that were downregulated. Few studies incorporated modern proteomic or transcriptomic techniques. Risk of bias was low with a mean Newcastle-Ottawa scale score of 7.0 (±0.6). Molecules associated with invasion were related to epithelial-mesenchymal transition (E-cadherin, ESRP1, fascin-1, and MMP-9), cellular proliferation (PTTG, AIP, TCERG1, EIF2β, E2F1, Notch 2, STAT3, ARRB1, TGFB1, SMAD3, SOX9, SGK1, MAGEA6 DLL3, EGFL7, and pEGFR), hormonal signalling (GNAS, DRD5, DRD1, sst5TMD4, SSTR2, and SSTR5), and tumour angiogenesis (VEGF and Drp1). These molecular variations present a possible explanation for the proclivity of somatotropinomas for the cavernous sinus. Identified molecules represent options for novel targeted therapies or biomarkers that could inform prognostication. Modern proteomic and transcriptomic techniques and larger somatotropinoma datasets are required to further elucidate the molecular pathways responsible for cavernous sinus invasion in somatotropinomas.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701352","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":"Mobile elements in pituitary neuroendocrine tumors: integrative evidence and future directions.","authors":"Rafael Loch Batista, Nathália Da Roz D'Alessandre, Flora Ladeira Craveiro, Juliana Moreira Marques, Elisa França Chaves, Gabriel Arantes Dos Santos, Gabriela Der Agopian Guardia, Pedro Alexandre Favoretto Galante","doi":"10.1530/ERC-25-0539","DOIUrl":"10.1530/ERC-25-0539","url":null,"abstract":"<p><p>Mobile genetic elements (MGEs), including LINE-1 retrotransposons, Alu and SVA elements, and human endogenous retroviruses (HERVs), constitute nearly half of the human genome and are increasingly understood to influence multiple dimensions of cancer evolution. Yet, pituitary neuroendocrine tumors (PitNETs) remain almost absent from mobilome research, despite exhibiting genomic and epigenetic contexts permissive to retroelement activation. In this review, we synthesize current evidence linking MGEs to PitNET biology and delineate unresolved but testable mechanisms. Structural genomic studies demonstrate that Alu-mediated non-allelic homologous recombination contributes to germline mutagenesis in MEN1 and AIP, reinforcing the notion that repetitive DNA architecture shapes PitNET predisposition. Transcriptomic analyses reveal global derepression of transposable elements and LINE-1 hypomethylation in subsets of tumors, while mechanistic connections to chromatin instability emerge from recurrent ATRX/DAXX deficiency and TP53 inactivation, both established repressors of retroelements. Furthermore, the retrocopy-derived long non-coding RNA RPSAP52 exemplifies how mobilome-origin transcripts can be co-opted as oncogenic regulators in PitNETs, acting through HMGA2-dependent proliferative networks. Preliminary data also suggest endogenous retroviral activation, with consistent upregulation of HERV envelope genes across distinct tumor subtypes. Nevertheless, no study has yet systematically mapped somatic mobile-element insertions (MEIs), quantified LINE-1 protein activity, or profiled HERV expression at locus resolution in PitNETs. Mobilome biology represents a tractable and conceptually rich frontier with diagnostic, prognostic, and therapeutic potential in pituitary tumorigenesis.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792783","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}