Endocrine-related cancer最新文献_第5页

Transforming thyroid cancer management: the impact of neoadjuvant therapy. 甲状腺癌治疗的变革：新辅助治疗的影响。

Endocrine-related cancer Pub Date : 2025-03-08 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0185

Inés Califano, Gregory Randolph, Fabián Pitoia

{"title":"Transforming thyroid cancer management: the impact of neoadjuvant therapy.","authors":"Inés Califano, Gregory Randolph, Fabián Pitoia","doi":"10.1530/ERC-24-0185","DOIUrl":"10.1530/ERC-24-0185","url":null,"abstract":"Neoadjuvant therapy has an emerging role in the management of locally advanced thyroid cancer. Recent developments in systemic therapies, particularly with the introduction of multikinase inhibitors and selective inhibitors, have demonstrated promising results. The objective of this review is to delve into the implications of these developments and their potential impact on the management of advanced thyroid cancers, which initially present as borderline resectable or unresectable. For differentiated thyroid cancer and poorly differentiated thyroid cancer, agents such as lenvatinib have shown substantial tumor reduction, facilitating surgical resection. Similarly, for medullary thyroid cancer, selpercatinib have exhibited interesting response rates, enhancing the feasibility of surgery with reduced morbidity in limited clinical case series of patients with RET mutations. In BRAF mutant ATC, the combination of BRAF and MEK inhibitors has significantly improved treatment protocols, providing a pathway to surgical intervention and significantly improving survival rates. The addition of immune checkpoint inhibitors to these regimens showed further extension of survival and reduced recurrence rates in retrospective studies that still need confirmation. Despite these preliminary favorable results, neoadjuvant therapies are not without challenges. The risk of adverse events, particularly related to the inhibition of the VEGF pathway, necessitates careful patient selection and management. The variability in tumor responses and the potential for serious complications underscore the need for continued research to refine these approaches in this difficult patient population.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443050","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}

引用次数: 0

Divergent PTEN-p53 interaction upon DNA damage in a human thyroid organoid model with germline PTEN mutations. 不同PTEN-p53相互作用对生殖系PTEN突变的人甲状腺类器官模型DNA损伤的影响

Endocrine-related cancer Pub Date : 2025-03-08 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0216

Juan Andres Venegas, Omer Enes Onur, Shin Chung Kang, Masahiro Hitomi, Charis Eng

{"title":"Divergent PTEN-p53 interaction upon DNA damage in a human thyroid organoid model with germline PTEN mutations.","authors":"Juan Andres Venegas, Omer Enes Onur, Shin Chung Kang, Masahiro Hitomi, Charis Eng","doi":"10.1530/ERC-24-0216","DOIUrl":"10.1530/ERC-24-0216","url":null,"abstract":"Germline mutations in the tumor suppressor phosphatase and tensin homolog (PTEN) cause PTEN hamartoma tumor syndrome (PHTS). PHTS is characterized by an elevated lifetime risk of differentiated thyroid cancer (DTC), 30 times higher than the general population. However, only 1 in 3 PHTS patients develop DTC, and it remains unknown whether specific PTEN variants are associated with an increased risk of DTC. PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway, a frequently affected pathway in sporadic DTC. PTEN also acts as a guardian of the genome by interacting with other tumor suppressors. Here, we report how ionizing radiation, an environmental tumorigenic contributor, modifies the DNA damage response based on the type of germline PTEN variants. We hypothesized that certain PTEN variants associated with DTC create a pro-oncogenic molecular signature upon radiation-induced DNA damage. DTC-associated (PTEN M134R ) or DTC-non-associated (PTEN G132D ) germline PTEN mutant alleles were introduced into a human induced pluripotent cell (hiPSC) line derived from a healthy donor utilizing CRISPR-Cas9 gene editing technology. We determined radiation-induced transcriptomic changes in functional thyroid organoids induced from wild-type and both heterozygous PTEN mutant hiPSCs. Both bulk and single-cell RNA sequencing data indicated that radiation upregulated the p53 network more potently in the thyroid organoids with PTEN WT/G132D than those with PTEN WT/M134R , which could be mediated by AKT-dependent MDM2 inactivation and PTEN-p53 physical interaction. Our data suggest that the lack of p53 pathway activation through PTEN-p53 network interactions explains why PTEN M134R is a DTC-susceptible variant.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461091","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}

引用次数: 0

Metabolically active brown adipose tissue in PPGL: an observational cohort study. PPGL中代谢活跃的棕色脂肪组织：一项观察性队列研究。

Endocrine-related cancer Pub Date : 2025-03-07 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0200

Eduard Oštarijaš, Michael C Onyema, Zoulikha Zair, David R Taylor, Fannie Lajeunesse-Trempe, Saira Reynolds, Nicola Mulholland, Ben Corcoran, Mohamed Halim, Eftychia E Drakou, Ashley B Grossman, Royce P Vincent, Simon J B Aylwin, Georgios K Dimitriadis, Silvija Canecki-Varžić

{"title":"Metabolically active brown adipose tissue in PPGL: an observational cohort study.","authors":"Eduard Oštarijaš, Michael C Onyema, Zoulikha Zair, David R Taylor, Fannie Lajeunesse-Trempe, Saira Reynolds, Nicola Mulholland, Ben Corcoran, Mohamed Halim, Eftychia E Drakou, Ashley B Grossman, Royce P Vincent, Simon J B Aylwin, Georgios K Dimitriadis, Silvija Canecki-Varžić","doi":"10.1530/ERC-24-0200","DOIUrl":"10.1530/ERC-24-0200","url":null,"abstract":"Brown adipose tissue (BAT) activity, identifiable through fluorodeoxyglucose positron emission tomography (FDG-PET), has gained interest due to its potential link with metabolic disorders and tumour pathophysiology. This study aims to explore the activation of BAT in patients with phaeochromocytoma/paraganglioma (PPGL) and its clinical relevance. This retrospective observational study, conducted in a large academic centre in London, reviewed FDG-PET images of 62 confirmed PPGL patients, collected between 2013 and 2021. We assessed patient demographics, biochemistry, radiological features, mutational status and outcomes, focussing on activated BAT detection. Of the 62 patients, 13% demonstrated active brown adipose tissue (aBAT) on FDG-PET imaging. Histopathological confirmation of BAT from one patient was used to validate BAT activation observed during imaging. Multivariate analysis indicated that elevated plasma normetanephrine concentrations were directly proportional to aBAT presence, suggesting their strong association with BAT activation. Despite identifying aBAT, no significant differences were found in BMI, sex, age or mutational status between aBAT-positive and aBAT-negative groups. Kaplan-Meier survival plots assessing overall and progression-free survival did not reach statistical significance. This study underscores the complex interaction between catecholamine excess and BAT activation in patients with PPGLs. The findings suggest that aBAT activity might be an indicator of severe catecholamine excess (especially normetanephrine), potentially influencing patient outcomes. Our study adds to the limited pool of knowledge and offers novel insights into BAT activation in patients with PPGLs, highlighting its potential link with metabolic derangements and patient outcomes.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477005","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}

引用次数: 0

Discordant risk factors between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinoma. 胰腺神经内分泌肿瘤与胰腺导管腺癌不一致的危险因素。

Endocrine-related cancer Pub Date : 2025-03-01 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0142

Shruti Chandra, Thorvardur R Halfdanarson, Erin E Carlson, Kari G Rabe, Amit Mahipal, Shounak Majumder, William R Bamlet, Masayasu Horibe, Sri Harsha Tella, Omair Shariq, Ryan M Carr, Sean P Cleary, Ann L Oberg, Samuel O Antwi

{"title":"Discordant risk factors between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinoma.","authors":"Shruti Chandra, Thorvardur R Halfdanarson, Erin E Carlson, Kari G Rabe, Amit Mahipal, Shounak Majumder, William R Bamlet, Masayasu Horibe, Sri Harsha Tella, Omair Shariq, Ryan M Carr, Sean P Cleary, Ann L Oberg, Samuel O Antwi","doi":"10.1530/ERC-24-0142","DOIUrl":"10.1530/ERC-24-0142","url":null,"abstract":"Pancreatic neuroendocrine neoplasm (panNEN) is a rare malignancy and the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma (PDAC), but its etiology is poorly understood. We investigated whether the risk factors of panNEN are concordant with those known for PDAC. We performed the largest case-control study to date on panNENs, comprising 927 sporadic nonfunctional panNEN cases and 1807 frequency-matched controls, using data from the Mayo Clinic Biospecimen Resource for Pancreas Research. We assessed associations for obesity, first-degree family history of pancreatic cancer, cigarette smoking, overall type II diabetes mellitus (T2DM), new-onset T2DM (<1 year before panNEN diagnosis), longstanding T2DM (≥5 years), alcohol intake and aspirin use. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). Our results show that overall T2DM (OR = 1.71, 95% CI: 1.37-2.14) and new-onset T2DM (OR = 2.65, 95% CI: 1.92-3.69) are associated with higher odds of panNEN, but not longstanding T2DM (OR = 1.29, 95% CI: 0.94-1.75). A non-significant elevated odds of panNEN was observed among participants with a positive family history of pancreatic cancer (OR = 1.44, 95% CI: 0.96-2.14). Alcohol use was inversely related to panNEN (OR = 0.52, 95% CI: 0.42-0.66, ever-vs-never). No association was observed for smoking, obesity or aspirin use. These findings indicate that overall T2DM and new-onset T2DM are associated with higher odds of panNEN. Unlike PDAC, alcohol use was inversely related to panNEN, and we found no associations for cigarette smoking, obesity or aspirin use. These results indicate differences in the risk factor profiles of panNEN and PDAC.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392774","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}

引用次数: 0

Local treatments and TKI efficacy in radioiodine refractory differentiated thyroid carcinoma patients: a single center experience. 放射性碘难治性分化甲状腺癌患者的局部治疗和TKI疗效：单中心经验。

Endocrine-related cancer Pub Date : 2025-03-01 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0024

Katerina Saltiki, Olga Karapanou, Kanella Kantreva, Marina Michalaki, Konstantinos Koutsoukos, Stavroula A Paschou, Maria Alevizaki

{"title":"Local treatments and TKI efficacy in radioiodine refractory differentiated thyroid carcinoma patients: a single center experience.","authors":"Katerina Saltiki, Olga Karapanou, Kanella Kantreva, Marina Michalaki, Konstantinos Koutsoukos, Stavroula A Paschou, Maria Alevizaki","doi":"10.1530/ERC-24-0024","DOIUrl":"10.1530/ERC-24-0024","url":null,"abstract":"A cohort of radioiodine-refractory differentiated thyroid cancer patients (RAI-R DTC) in a tertiary center underwent therapeutic interventions according to disease progression rate and metastasis location. We evaluated the independent impact of local and/or systemic treatments on final outcomes in 122 RAI-R DTC patients (44.3% men, age at diagnosis 51.98 ± 15.8 years) who were followed up for 9.5 years (1.4-50). Patients were divided into two groups: those with only locoregional persistent disease: group 1, n = 27 (22.1%) and those with distant metastases: group 2, n = 95 (77.9%). Patients from group 1 underwent mainly local procedures. The final outcome was 4/27 (14.8%) partial-response (PR) and 23/27 (85.2%) stable disease (SD). Of group 2 patients, 10/95 underwent active surveillance for micrometastatic disease, and the remaining received either only local treatments (40/95) or TKIs ± local treatments (45/95). The final outcome was PR in 7/95 (7.4%), SD in 38 (40%) and progressive disease in 50 (52.6%). Concerning group 2 in Kaplan-Meier analysis, local metastasis stabilization with local and/or systemic therapy had a favorable effect on survival (P < 0.02). Those treated with TKIs + local procedures, despite having more aggressive tumors, achieved more frequently local stabilization and had a similar outcome compared to those treated with only TKIs (P = 0.007). For group 2, in Cox proportional hazard analysis during the follow-up period, younger age at diagnosis and maintenance of tumor differentiation are predictors of more favorable OS and cancer-specific survival. In conclusion, the implementation of local procedures in RAI-R DTC management stabilizes metastatic lesions and potentially enhances survival. Further studies are warranted to validate these findings.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461022","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}

引用次数: 0

Real-world outcomes of lenvatinib therapy for advanced neuroendocrine neoplasms. lenvatinib治疗晚期神经内分泌肿瘤的实际结果。

Endocrine-related cancer Pub Date : 2025-02-24 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0292

Joao Paulo Solar Vasconcelos, Jose Eduardo Nunez Rodriguez, Ali Zaidi, Tharani Krishnan, Helia Jafari, Sharlene Gill, Ann Tan, Dan Le, Theresa Chan, Simon Yu, John Paul McGhie, Howard Lim, Simron Singh, Jonathan M Loree

{"title":"Real-world outcomes of lenvatinib therapy for advanced neuroendocrine neoplasms.","authors":"Joao Paulo Solar Vasconcelos, Jose Eduardo Nunez Rodriguez, Ali Zaidi, Tharani Krishnan, Helia Jafari, Sharlene Gill, Ann Tan, Dan Le, Theresa Chan, Simon Yu, John Paul McGhie, Howard Lim, Simron Singh, Jonathan M Loree","doi":"10.1530/ERC-24-0292","DOIUrl":"10.1530/ERC-24-0292","url":null,"abstract":"Advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a heterogeneous group of incurable cancers. Lenvatinib is an oral multiple kinase inhibitor that showed activity in grade 1/2 GEP-NENs in the phase II TALENT trial, but a confirmatory phase III study has yet to be conducted. To investigate the real-world use of lenvatinib in treating patients with advanced GEP-NENs, we retrospectively analyzed a cohort of adults with unresectable neuroendocrine neoplasms (NENs) from two academic centers in Canada who received palliative treatment with lenvatinib. Progression-free survival (PFS), overall survival (OS) and the treating clinician assessment of best therapeutic response were analyzed in the entire cohort and in the subgroup of patients with GEP-NENs that would have been eligible for the TALENT trial. Overall, 33 patients, with mostly G1/G2 (78.8%) metastatic NENs, received lenvatinib. The pancreas was the most common primary site (n = 16, 48.5%), followed by the small bowel (n = 12, 36.4%). The median number of prior lines of systemic therapy was 2 (range 1-5). The median initial, maximal and minimal doses (mg) were 12 (range 4-24), 12 (range 8-24) and 8 (range 4-24), respectively. The median PFS was 11.9 months (95% CI, 9.5-NA), and the median OS was 17.5 months (95% CI, 12.7-NA), with disease burden reduction seen in 21.9% (95% CI, 11.0-38.7) and 87.5% (95% CI, 71.9-95.3) of patients achieving disease control. The most frequent side effects reported were hypertension (60.6%), fatigue (39.4%), hypothyroidism (21.2%) and diarrhea (18.2%). This real-world cohort demonstrates encouraging evidence of lenvatinib activity in metastatic NENs, even when used at lower doses than previously studied in NENs.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384577","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}

引用次数: 0

Management of high-grade neuroendocrine neoplasms: impact of functional imaging. 高级别神经内分泌肿瘤的治疗：功能影像学的影响。

Endocrine-related cancer Pub Date : 2025-02-19 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0231

O Islam, K Sarti, L Verbruggen, V Vandersmissen, K Vanden Bulcke, L Annys, C Verslype, J L Van Laethem, H Rezaei Kalantari, J Janssens, A Hendlisz, P J Cuyle, G Demolin, J Decaestecker, K Geboes, J C Coche, J Van Ongeval, W Lybaert, M Peeters, I Borbath, T Vandamme

{"title":"Management of high-grade neuroendocrine neoplasms: impact of functional imaging.","authors":"O Islam, K Sarti, L Verbruggen, V Vandersmissen, K Vanden Bulcke, L Annys, C Verslype, J L Van Laethem, H Rezaei Kalantari, J Janssens, A Hendlisz, P J Cuyle, G Demolin, J Decaestecker, K Geboes, J C Coche, J Van Ongeval, W Lybaert, M Peeters, I Borbath, T Vandamme","doi":"10.1530/ERC-24-0231","DOIUrl":"10.1530/ERC-24-0231","url":null,"abstract":"Gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) exhibit substantial biological heterogeneity, impacting clinical management and outcomes. In 2019, the WHO subdivided the grade 3 (G3) neuroendocrine neoplasms (NEN) characterised by Ki-67 > 20% into the well-differentiated G3 neuroendocrine tumour (NET) and G3 poorly differentiated neuroendocrine carcinoma (NEC) subgroups. Since this update, questions about the prognostic implications and best treatment strategies for NET G3 and NEC remain. Therefore, we initiated a real-world retrospective observational cohort study using data from 225 NEC and 58 NET G3 patients treated in Belgium. Analysis of patient and tumour characteristics and the effect of survival was conducted. Most frequent primary locations were pancreatic (32.9%) and colorectal (21.5%), and 71.8% was diagnosed with stage IV disease. Median overall survival (mOS) was higher in NET G3 (41.3 months (m)) compared to NEC (13.2m). Of those who underwent functional imaging, fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging was positive in 90.6 and 95.6% of the NET G3 and NEC patients, respectively, and somatostatin receptor (SSTR) expression was seen in 97.4 and 66.0%, respectively. The latter was linked to better mOS, suggesting the added value of performing both SSTR imaging and 18F-FDG-PET for high-grade (HG) NEN to provide prognostic information and to possibly expand therapeutic options, which are currently reserved for lower-grade NEN patients. Moreover, while debated, in our population, primary surgery was performed in 92 and 73.5% of locoregional NET G3 and NEC cases, respectively, indicating that surgery can be considered in locoregional setting. Finally, platinum-etoposide was the predominant first-line treatment in metastatic NEC, with no significant survival difference between carboplatin and cisplatin.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070402","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}

引用次数: 0

Spectrum and carcinogenic properties of thyroglobulin gene fusions in thyroid. 甲状腺中甲状腺球蛋白基因融合的谱和致癌特性。

Endocrine-related cancer Pub Date : 2025-02-17 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0334

Gavin M Schmidt, Ian J Fornal, William R Doerfler, Abigail I Wald, Shannon E Keating, Marina N Nikiforova, Yuri E Nikiforov, Alyaksandr V Nikitski

{"title":"Spectrum and carcinogenic properties of thyroglobulin gene fusions in thyroid.","authors":"Gavin M Schmidt, Ian J Fornal, William R Doerfler, Abigail I Wald, Shannon E Keating, Marina N Nikiforova, Yuri E Nikiforov, Alyaksandr V Nikitski","doi":"10.1530/ERC-24-0334","DOIUrl":"10.1530/ERC-24-0334","url":null,"abstract":"Approximately 10-20% of thyroid cancers are driven by gene fusions, which activate oncogenic signaling through aberrant overexpression, ligand-independent dimerization or loss of inhibitory motifs. We identified 13 thyroid tumors with thyroglobulin (TG) gene fusions and aimed to assess their histopathology and the fusions' oncogenic and tumorigenic properties. Of eleven cases with surgical pathology, 82% were carcinomas and 18% were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). TG fusions preserved exon(s) 1, 1-15, 1-35 or most frequently, 1-47 of TG and, based on the 3' partner were grouped as i) involving receptor tyrosine kinases (RTKs) (TG::FGFR1, TG::RET, TG::ALK and TG::NTRK1), ii) driving aberrant DPRX and chromosome 19 microRNA cluster expression (TG::DPRX) or iii) involving IGF2 mRNA-binding protein (TG::IGF2BP1). All 13 fusion-positive tumors exhibited strong (8.5 ± 3.3 log2-fold) 3' partner overexpression driven by the TG promoter. Gene expression analysis revealed TG::RET- and TG::ALK-positive tumors being BRAFV600E-like and remaining tumors RAS-like. In thyroid PCCL3 cells, the TG::NTRK1 fusion demonstrated both spontaneous and ligand-associated dimerization, activated downstream MAPK, AKT and STAT3 signaling and drove xenograft tumorigenesis in nude mice. FDA-approved NTRK inhibitors entrectinib and larotrectinib effectively blocked TG::NTRK1 signaling in vitro and inhibited xenograft tumor growth in vivo. In summary, we report a spectrum of TG gene fusions as recurrent oncogenic events in thyroid cancer and NIFTP that drive strong overexpression of partner genes, frequently RTKs. The TG::NTRK1 fusion is prone to dimerization, activates oncogenic signaling, drives tumorigenesis in thyroid cells and, like other fusions involving RTKs, represents a potential therapeutic target in thyroid cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061726","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}

引用次数: 0

Development and validation of long-acting recombinant human TSH using SAFA technology. 利用SAFA技术开发和验证长效重组人TSH。

Endocrine-related cancer Pub Date : 2025-02-17 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0284

Daham Kim, Min Jeong Kang, So Jeong Lee, Yoon Hee Cho, Gunuk Zi, Jeongsuk An, Jinjoo Park, Jaekyu Han, Susan Chi, Sang-Hoon Cha, Eun Jig Lee

{"title":"Development and validation of long-acting recombinant human TSH using SAFA technology.","authors":"Daham Kim, Min Jeong Kang, So Jeong Lee, Yoon Hee Cho, Gunuk Zi, Jeongsuk An, Jinjoo Park, Jaekyu Han, Susan Chi, Sang-Hoon Cha, Eun Jig Lee","doi":"10.1530/ERC-24-0284","DOIUrl":"10.1530/ERC-24-0284","url":null,"abstract":"Thyrogen, a recombinant human thyroid-stimulating hormone (rhTSH), has a short half-life in the bloodstream, which necessitates multiple doses during treatment. Therefore, we developed a new long-acting rhTSH using anti-serum albumin Fab-associated (SAFA) technology to validate its biological activity through in vitro assays, pharmacokinetic studies in healthy mice and pharmacodynamics studies in a thyroid-stimulating hormone (TSH)-suppressed mouse model. SAFA-TSH was produced using a Chinese hamster ovary expression system. To verify its biological activity, we generated Nthy-ori 3-1 cells stably overexpressing TSHR and measured the production of cyclic adenosine monophosphate (cAMP). In a rat study, slow-release triiodothyronine (T3) pellets were implanted 3 days before administering Thyrogen or SAFA-TSH to measure the amount of thyroxine (T4) release alone resulting from exogenous administration. SAFA-TSH increased cAMP production dose-dependently, but less effectively than Thyrogen at similar concentrations. SAFA-TSH required six times the dose of Thyrogen to achieve similar cAMP levels, likely due to differences in molecular weight and relative bioactivity. In a rat study, SAFA-TSH produced elevated thyroid hormone levels well after the decline in the response to Thyrogen. SAFA-TSH had significantly higher cumulative effects on T4 and free T4 levels compared with Thyrogen, as observed by a more than two-fold higher average area under the effect curve of 262.56 vs 118.89 μg × h/dL and 127.47 vs 60.75 μg × h/dL, respectively. SAFA technology created successful long-acting TSH that demonstrated bioactivity. These findings endorse the continued development of SAFA-TSH for clinical use, highlighting its potential as a significant advancement treating thyroid cancer patients.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191629","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}

引用次数: 0

Global trends in thyroid cancer 1990-2021: an analysis based on the GBD 2021. 1990-2021年全球甲状腺癌趋势：基于GBD 2021的分析

Endocrine-related cancer Pub Date : 2025-02-12 Print Date: 2025-03-01 DOI: 10.1530/ERC-24-0297

Tong Deng, Qing Liu, Hao Zi, Xingpei Guo, Qiao Huang, Yalong Yang, Lisha Luo, Jingxuan Hou, Rui Zhou, Qianqian Yuan, GaoSong Wu

{"title":"Global trends in thyroid cancer 1990-2021: an analysis based on the GBD 2021.","authors":"Tong Deng, Qing Liu, Hao Zi, Xingpei Guo, Qiao Huang, Yalong Yang, Lisha Luo, Jingxuan Hou, Rui Zhou, Qianqian Yuan, GaoSong Wu","doi":"10.1530/ERC-24-0297","DOIUrl":"10.1530/ERC-24-0297","url":null,"abstract":"This study evaluated the global burden of thyroid cancer (TC) from 1990 to 2021, analyzing its association with sociodemographic factors, sex, age, risk factors and future projections. Using 2021 global burden of disease data, we analyzed TC incidence, mortality and disability-adjusted life years (DALYs) across populations. Risk factors were assessed, and future trends were forecasted using the Bayesian age-period-cohort model. In 2021, global TC incidence was 249,538 cases (age-standardized incidence rate (ASIR): 2.91 per 100,000). Mortality reached 44,799 cases, with a slight decrease in the age-standardized mortality rate (ASMR). DALYs increased by 92.73%, though the age-standardized DALY rate (ASDR) declined. East Asia had the highest incidence, while South Asia led in mortality and DALYs. TC burden showed a strong negative correlation with socioeconomic development, especially in high- and medium-sociodemographic index countries. High body mass index (BMI) contributed significantly to DALYs and mortality, particularly in the Middle East and North Africa. Population growth emerged as the key driver of the rising global TC burden. Projections suggest ASIR will increase by 2050, while ASMR and ASDR will decline. Global TC incidence has risen markedly, particularly among males, while mortality and DALYs have decreased due to improved healthcare. High BMI increasingly contributes to the TC burden. Projections highlight a continued rise in incidence but declining mortality and DALYs, reflecting advancements in treatment and management.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061689","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}

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