Endocrine-related cancer最新文献

{"title":"Anlotinib in progressive RAI-refractory differentiated thyroid cancer: long-term results and PET/CT prognostic markers.","authors":"Di Sun, Xin Zhang, Yingqiang Zhang, Cong Shi, Xiaona Jin, Yuqing Sun, Jun Liang, Yansong Lin","doi":"10.1530/ERC-25-0027","DOIUrl":"10.1530/ERC-25-0027","url":null,"abstract":"<p><p>The efficacy and tolerability of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC), especially those with prior VEGFR-targeted therapies, are not fully understood. This study reported the long-term outcomes of anlotinib-treated progressive RAIR-DTC patients and evaluated the prognostic value of 68Ga-NOTA-3PRGD2 and 18F-FDG PET/CT parameters. In this open-label, single-arm, single-center, prospective trial, 20 progressive RAIR-DTC patients were enrolled to receive anlotinib (orally once daily on days 1-14 every 3 weeks). The study endpoints included long-term efficacy and safety. The association between PET/CT parameters at baseline and 6-week assessments and progression-free survival (PFS) was also investigated. The median PFS was 22.5 (95% CI, 16.8-27.9) months, the estimated median overall survival was 38.4 (95% CI, 20.4-56.4) months, the overall response rate was 47.4% (95% CI, 24.4-71.1), the disease control rate was 89.5% (95% CI, 66.9-98.7), and the median time to response was 4.1 (range, 1.3-8.4) months. There were no significant differences in clinicopathological, efficacy, and safety markers between patients with prior VEGFR-targeted agents (treated group, n = 10) or those without (naïve group, n = 10) (P > 0.05). Higher baseline integrin-expressing tumor burden on 68Ga-NOTA-3PRGD2 PET/CT and glucose metabolic progression on 18F-FDG PET/CT 6 weeks after anlotinib treatment were both associated with shorter PFS. Anlotinib showed promise as an effective treatment option for both initial and salvage therapy in progressive RAIR-DTC patients. Integrin- and glucose metabolic-based PET/CT parameters showed predictive potential in anlotinib-treated patients and warrant further study.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839506","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":"Rising incidence of follicular thyroid carcinoma and oncocytic carcinoma of the thyroid in Australia.","authors":"Steven Weller, Cordia Chu, Alfred King-Yin Lam","doi":"10.1530/ERC-24-0326","DOIUrl":"10.1530/ERC-24-0326","url":null,"abstract":"<p><p>The incidence of follicular thyroid carcinoma (FTC) and oncocytic carcinoma of the thyroid has seldom been studied. However, thyroid cancer incidence has experienced significant increases globally over recent decades. This study aims to investigate the incidence of FTC and oncocytic carcinoma of the thyroid in Australia with particular attention to the impact of changes in the World Health Organization (WHO) endocrine tumour classification. Using incidence data from the Australian Institute of Health and Welfare cancer registry (spanning 1982-2019), this descriptive epidemiological study employed joinpoint regression analysis to assess temporal trends in FTC and oncocytic carcinoma of the thyroid. Results were then compared with WHO endocrine tumour classification changes over the same period to identify potential impact(s). FTC and oncocytic carcinoma of the thyroid accounted for 9.4 and 3.2% respectively, of all thyroid carcinomas. Oncocytic carcinoma of the thyroid incidence steadily increased across the study period. Subtype analysis of FTC showed the incidence of widely invasive FTC initially increased significantly before declining and was found to affect older adults primarily. On the other hand, minimally invasive FTC incidence rose sharply for both sexes. Encapsulated angioinvasive FTC, a recently classified subtype, was found predominantly in younger age groups, particularly the 30-34 age bracket. Changes in the incidence of FTC and oncocytic thyroid carcinoma are noted to be influenced by classification updates. To conclude, there is a steady rise in Australian FTC and oncocytic carcinoma of the thyroid incidence, influenced to some degree by WHO classification changes.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823458","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":"Survival following resection of 10,244 lung neuroendocrine tumours: a population study.","authors":"Marie Line El Asmar, Mohamed Mortagy, Benjamin E White, John Ramage","doi":"10.1530/ERC-25-0211","DOIUrl":"10.1530/ERC-25-0211","url":null,"abstract":"<p><p>Surgical resection is the primary treatment for lung neuroendocrine tumours (NET) but the optimal follow-up is unclear. This is a population-based analysis of 3,307 patients from England (NCRAS database; 2012-2021) and 6,937 patients from the United States (SEER database; 2003-2022) who underwent surgical resection for lung NET, which explores factors affecting post-surgical survival and optimal follow-up duration in these patients. Kaplan-Meier (KM) analysis estimated overall survival (OS). Cox proportional hazards models identified factors affecting survival. Patients were matched to national life tables (UK and US) by age, sex, and year of diagnosis to compare actual versus expected KM plots. In NCRAS, OS at 1, 3, 5, and 10 years was 99.6, 95.3, and 91.2% respectively, and in SEER 99.7, 95.5, and 91.8% respectively. In both England and the US, most patients presented with stage 1 disease. Multivariable Cox regression analyses showed that increasing age, advanced stage, socioeconomic deprivation, and atypical carcinoid morphology were associated with worse survival in both countries. In addition, in the US, male sex and pneumonectomy or wedge resection were also associated with worse survival. No overlap was observed between actual and expected KM plots in England, either overall or in subgroups of stage 1, typical morphology, or tumour <2 cm. In the US, an overlap was observed between actual and expected KM plots for the overall cohort at 240 months (20 years). This analysis of two large national cohorts provides information on the survival of lung NET after surgery, which can contribute to future guideline development on long-term follow-up.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796490","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":"Locoregional progression and surgical indications in stage IV asymptomatic SI-NETs.","authors":"Branislav Klimácek, Tobias Åkerström, Matilda Annebäck, Per Hellman, Staffan Welin, Anders Sundin, Olov Norlén, Peter Stålberg","doi":"10.1530/ERC-25-0205","DOIUrl":"10.1530/ERC-25-0205","url":null,"abstract":"<p><p>Small intestinal neuroendocrine tumors are often diagnosed at an advanced stage, with up to 70% of patients presenting with stage IV disease. While some guidelines recommend prophylactic resection of the primary tumor and mesenteric lymph node metastasis in patients without abdominal symptoms at diagnosis to prevent future abdominal complications, the benefit of this approach remains uncertain. This retrospective cohort study included 44 asymptomatic patients with stage IV small intestinal neuroendocrine tumors treated at Uppsala University Hospital between 2014 and 2019. Additional ten symptomatic patients who underwent at least two computed tomography scans before planned surgery were included in the analysis of mesenteric metastasis volume change and tumor growth rate. The primary outcomes were abdominal symptoms development requiring surgical intervention and the assessment of mesenteric metastasis size progression. During a 10-year follow-up, only four initially asymptomatic patients (9%) developed symptoms leading to surgery. Among all 54 patients, the median volume change in mesenteric metastases was -298 mm3 (IQR: -2,785-1,294), with no significant difference between baseline and most recent scans (P = 0.38). The median interval between scans was 29 months, and the median tumor growth rate was -0.6% per month (IQR: -3.6-1.9%). Similar results were observed in the asymptomatic group. These findings suggest that a non-operative management in stage IV patients without abdominal symptoms is associated with a low incidence of symptom development and limited progression of mesenteric metastases.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786246","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":"Heme-oxygenase-1: a key player in thyroid carcinoma development.","authors":"Exequiel Gonzalo Alonso, Marilina Mascaró, Karen Schweitzer, Gisela Giorgi, Jessica Andrea Carballido, Agustina Ibarra, Valentina Clemente, Pamela Pichel, Sergio Recio, Lucía Fernández Chávez, Georgina Pamela Coló, Eliana Noelia Alonso, María Julia Ferronato, María Eugenia Fermento, María Marta Facchinetti, Alejandro Carlos Curino","doi":"10.1530/ERC-25-0177","DOIUrl":"10.1530/ERC-25-0177","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Thyroid cancer is the most prevalent type of endocrine malignancy. Papillary thyroid carcinoma represents the majority of cases and is curable in approximately 90% of them, but it may also progress to anaplastic thyroid cancer, which has a poor prognosis. Therefore, the identification of new therapeutic targets remains essential. In clinical practice, HO-1 mRNA is used as a biomarker to predict malignancy in thyroid nodules. However, its role in thyroid tumor progression remains understudied, as well as its potential as a therapeutic target. In this work, we confirmed that HO-1 protein is increased in human papillary thyroid cancer tissues and further demonstrated that high HO-1 mRNA is associated with progression to anaplastic thyroid cancer. Through pharmacological modulation of human papillary and anaplastic thyroid cells, and by genetically overexpressing HO-1 variants in papillary thyroid cells, we demonstrated that the overexpression of enzymatically active HO-1 enhances cell proliferation, migration, and cell cycle progression. Finally, we demonstrated that MEK/ERK signaling is partially involved in HO-1 effects. We concluded that HO-1 plays a relevant protumor role in thyroid cancer, and it may be a promising coadjuvant therapeutic target for papillary and anaplastic thyroid cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755490","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":"Systems biology successes and areas for opportunity in prostate cancer.","authors":"Michael V Orman, Laura S Graham, Scott D Cramer, James C Costello","doi":"10.1530/ERC-25-0067","DOIUrl":"https://doi.org/10.1530/ERC-25-0067","url":null,"abstract":"<p><p>Systems biology approaches have been applied to prostate cancer to model how individual cellular and molecular components interact to influence cancer development, progression, and treatment responses. The integration of multi-omic experimental data with computational models has provided insights into the molecular characteristics of prostate cancer and emerging treatment strategies that have the potential to improve patient outcomes. Here, we highlight recent advancements that have emerged from systems modeling in prostate cancer. These include descriptions of the molecular landscape of prostate cancer and how genomic alterations inform computational models of disease progression, how evolutionary processes give rise to mechanisms of therapeutic resistance, and the development of innovative treatment strategies such as adaptive therapy. We also highlight current challenges in prostate cancer that can be addressed through systems biology approaches. These include tumor heterogeneity, poor immunotherapy response, a paucity of experimental model systems, and the ongoing translation of computational models for clinical decision making. Leveraging systems biology approaches has the potential to lead to a better understanding of the disease and better patient outcomes in the treatment of prostate cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983779","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":"Targeting RET in medullary thyroid cancer.","authors":"Kate Newbold, Leslie Cheng","doi":"10.1530/ERC-24-0291","DOIUrl":"10.1530/ERC-24-0291","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Medullary thyroid cancer (MTC) is a rare cancer, accounting for 2-3% of all thyroid cancers. Point mutations in the RET proto-oncogene can be detected in 25-65% of MTC. These mutations commonly occur in the cysteine-rich or tyrosine kinase domains, leading to constitutively active tyrosine kinase activity in RET. In the last decade, significant advancements have been made in treating MTC with the advent of tyrosine kinase inhibitors, especially in RET-mutated MTC. Multikinase inhibitors such as vandetanib and cabozantinib were the first few effective inhibitors, which have been shown to slow disease progression in the treatment of advanced MTC. In more recent years, these have been followed by highly selective RET inhibitors selpercatinib and pralsetinib, which have made their way into the clinic, demonstrating high efficacy and a more favourable side-effect profile due to their reduction in off-target effects. In spite of these successes, there remains a continued need to develop strategies to overcome treatment resistance.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755491","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":"Lenvatinib as salvage therapy in advanced and progressive GI-NET.","authors":"Annie Mathew, Jaume Capdevila, Nicole Unger, Wolfgang Fendler, Sarah Theurer, Frank Weber, Dagmar Fuhrer, Harald Lahner","doi":"10.1530/ERC-25-0165","DOIUrl":"10.1530/ERC-25-0165","url":null,"abstract":"<p><p>The efficacy of lenvatinib in treating gastrointestinal neuroendocrine tumors (GI-NETs) has been explored in preclinical studies and early-phase clinical trials, but real-world data remain limited. Data of sixteen patients (median age 65 years; 62.5% female) with advanced and progressive GI-NET who were treated with lenvatinib at the ENETS Center, University Hospital Essen, between July 2019 and February 2024 were analyzed. Patients received all other approved therapies and showed progression within 2 months. Salvage therapy with lenvatinib was initiated after approval from health insurance. Most NETs originated in the small intestine (94%) with a median Ki-67 index of 3.5%. Before lenvatinib, patients received a median of four lines of treatment (range 3-7), including somatostatin analogs (100%), everolimus (100%), chemotherapy (25%) and PRRT (88%). Surgery of the primary and/or metastatic lesions was performed in 81% and ablative therapies in 38%. The median time between NET diagnosis and the initiation of lenvatinib was 100 months. The overall response rate on salvage therapy was 29% and the clinical benefit rate was 100%. The median progression-free survival (PFS) on lenvatinib was 10 months and the median overall survival (OS) after the initiation of lenvatinib reached 113 months. Hypertension was associated with significantly longer PFS (24.5 months, P = 0.007), whereas weight loss correlated with shorter PFS (4 months, P = 0.0032). In this retrospective single-center case analysis, lenvatinib demonstrated promising results in heavily pre-treated and rapidly progressing GI-NET. With an OS of 9.4 years after start of salvage therapy, these results highlight the value of lenvatinib as a therapeutic option for advanced GI-NET patients with otherwise limited treatment alternatives.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762759","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":"Targeting Src tyrosine kinase to enhance radioiodide uptake in breast cancer.","authors":"Vikki L Poole, Mohammed M Alshahrani, Selvambigai Manivannan, Iñigo Landa, Aditi Hariharan, Rebecca J Thompson, Merve Kocbiyik, Caitlin E M Thornton, Katie Brookes, Alice Fletcher, Kristien Boelaert, Martin L Read, Christopher J McCabe, Vicki E Smith","doi":"10.1530/ERC-24-0312","DOIUrl":"10.1530/ERC-24-0312","url":null,"abstract":"<p><p>Sodium iodide symporter (NIS) expression in breast cancer renders radioiodide (RAI) a promising treatment modality. However, insufficient functional NIS within the plasma membrane limits RAI uptake (RAIU). We aimed to elucidate NIS regulatory mechanisms that impede RAIU in breast cancer and identify molecular targets for stimulating RAI-avidity in breast tumours. Mechanistic interaction between pituitary tumor-transforming gene-binding factor (PBF/PTTG1IP) and NIS was investigated through NanoBiT, co-immunoprecipitation, immunofluorescent microscopy, subcellular localisation and RAIU assays utilising wild-type and CRISPR-Cas9 PBF knockout breast cancer cells. In breast cancer cells, NIS:PBF interaction resulted in diminished RAIU, reversible through reduced PBF phosphorylation by the Src inhibitor dasatinib. Src overexpression diminished RAIU in a PBF-dependent manner that was mediated by Src myristoylation by N-myristoyltransferase 1 (NMT1). NMT1 inhibition significantly enhanced RAIU via Src and PBF in breast and thyroid cancer cells. Bioinformatic analyses revealed clinical associations between high Src and NMT1 expression and increased tumour recurrence in RAI-treated thyroid cancers indicating RAI-resistance. In breast cancer, high PBF and Src expression was associated with the more aggressive tumours that are most likely to benefit from targeted RAI therapy. We describe a new NIS regulatory pathway in breast cancer cells via Src myristoylation and PBF phosphorylation and show that the same pathway exists in thyroid cells, the canonical setting for the exploitation of NIS function. These findings reveal that PBF interaction with NIS may be modulated by Src, which in turn is susceptible to NMT inhibition, and suggest that targeting NMT1 may represent an innovative approach for augmenting RAI-avidity in breast cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762760","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":"DNA-PKcs inhibition as a therapeutic approach for differentiated thyroid cancer.","authors":"Shu-Fu Lin, Wei-Yi Chen, Chuen Hsueh, Ting-Chao Chou, Richard J Wong","doi":"10.1530/ERC-25-0031","DOIUrl":"10.1530/ERC-25-0031","url":null,"abstract":"<p><p>DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a serine-threonine protein kinase that plays critical roles in cellular processes fundamental to cancer. DNA-PKcs may be a potential target for differentiated thyroid cancer (DTC) therapy. A DNA-PKcs inhibitor, M3814, was evaluated for its use in DTC therapy. M3814 caused cytotoxicity in a dose-response fashion in four DTC cell lines (TPC1, K1, FTC-133, and FTC-238). M3814 induced cell cycle arrest at the S phase in DTC cells. M3814 monotherapy was able to repress the growth of the K1 tumor model. M3814 in combination with lenvatinib demonstrated synergism in vitro, and this combination was more effective than any single therapy in an FTC-133 xenograft model. These results reveal that M3814 has significant potential in treating DTC, singly or in drug combination.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677052","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}