Endocrine oncology (Bristol, England)最新文献

{"title":"Characterisation of a <i>GNAS</i> variant linked to cortisol-producing adrenocortical adenoma.","authors":"Aqfan Jamaluddin, Rachael Wyatt, Andreea Pasaliu, Oliver Ruggles, Davide Calebiro, Caroline M Gorvin, Cristina L Ronchi","doi":"10.1530/EO-25-0009","DOIUrl":"10.1530/EO-25-0009","url":null,"abstract":"<p><strong>Objective: </strong>Adrenocortical adenomas are frequent in the general population and can be associated with autonomous cortisol excess, increasing morbidity and mortality. Altered cAMP/PKA signalling is common in sporadic cortisol-producing adenomas, typically due to somatic activating mutations in the catalytic subunit α of PKA (<i>PRKACA</i>) or the G-protein α subunit, Gα_s (<i>GNAS</i>), which activate cAMP signalling. We previously identified a novel p.Lys58Gln <i>GNAS</i> somatic variant in a patient with a 5.3 cm adenoma and overt Cushing's syndrome. This novel mutation was not charactersised before but provided enough evidence to warrant further investigation.</p><p><strong>Design and methods: </strong>Using HEK293 cells depleted of <i>GNAS</i>, we established wild-type (WT) Gα_s and Gα_s-Lys58Gln stable cell lines and evaluated adrenocorticotropic hormone (ACTH) receptor signalling using a cAMP GloSensor assay, measured CREB transcription factor phosphorylation (pCREB) by AlphaLISA and assessed <i>CRE</i> luciferase reporter activity. Cell viability and apoptosis were also assessed over 5 days.</p><p><strong>Results: </strong>The Gα_s-Lys58Gln variant showed a significantly higher basal cAMP, pCREB and <i>CRE</i> luciferase reporter concentration and a greater response to ACTH (0-10 nM, <i>P</i> < 0.001) compared to WT Gα_s. The variant had no effect on ligand potency. There was also significantly enhanced cell viability and apoptosis in cells with the Gα_s-Lys58Gln variant.</p><p><strong>Conclusions: </strong>In conclusion, our study demonstrated that the Gα_s-Lys58Gln variant is associated with constitutive activation of GNAS signalling, similar to Arg201 mutations previously reported in adrenocortical adenomas, potentially representing a new pathogenic mechanism in a subset of patients with adrenal Cushing syndrome. This variant may also affect cell proliferation and requires further study.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e250009"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103263","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":"Diagnosis and management of brain metastasis from thyroid cancer.","authors":"Vincent Cascio, W Reed Doerfler, Charit Taneja","doi":"10.1530/EO-25-0002","DOIUrl":"10.1530/EO-25-0002","url":null,"abstract":"<p><p>The brain is an uncommon location for metastatic spread from thyroid cancer. Given the rarity of the condition, the data regarding various management options for such patients are suboptimal. Radioactive iodine is seldom useful for brain metastases owing to variable uptake and unclear benefit. Surgical resection and stereotactic radiation remain the first-line treatment options for a limited number of brain metastases from thyroid cancer, as they not only provide local control and symptomatic relief but can also improve survival. Whole-brain radiation therapy has been used for patients with multiple brain metastases but has largely fallen out of favor due to the availability of more targeted and tolerable options. Systemic therapy with kinase inhibitors is a novel and promising area of research in this field, with an increased utilization of molecular testing to identify targetable mutations. Treatment plans for patients with brain metastases from thyroid cancer should be highly individualized and tailored to the specific patient by a multidisciplinary care team.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e250002"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103198","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":"Validity of geographic-level social determinant of health metrics in pancreatic neuroendocrine tumors.","authors":"Andrea Gillis, Brendon Herring, Rachael Guenter, Weisheng Chen, Dai Chen, Herbert Chen, John Bart Rose, Upender Manne, Smita Bhatia","doi":"10.1530/EO-25-0029","DOIUrl":"10.1530/EO-25-0029","url":null,"abstract":"<p><p>Various social determinants of health (SDOH) metrics, also known as area-based social measures, are utilized to evaluate access to cancer care and to explain disparities in outcomes. Little prior work has compared the validity of these various geographic metrics. We reviewed all patients surgically treated for PNETs (2006-2022) at a single comprehensive cancer center. We collected patient demographics including self-reported race (White or Black), billing addresses, tumor characteristics and area-based social measures. We then compared between- and within-race differences to understand accuracy across different geographic levels. One hundred seventy-nine patients were included; 49 (27%) Black, a median age of 60.3 years and 86 (48%) females. At the block group/census tract level, compared to White patients, Black patients lived in neighborhoods with lower educational attainment, lower income, higher rates of uninsurance, higher overall social vulnerability index (SVI), and higher area deprivation index (ADI) (all <i>P</i> < 0.05). These differences, however, were masked when examining county-level area-based social measures. Compared to census block group/tract-level data, for White patients, zip code-level metrics underestimated income and overestimated uninsurance level (<i>P</i> < 0.05). County-level metrics underestimated White patients' income and education level but overestimated poverty, uninsurance rate and SVI (all <i>P</i> < 0.05). For Black patients, zip code-level metrics overestimated poverty and uninsurance rates (<i>P</i> < 0.05); the only inaccurate county-level metric was overestimation of SVI (<i>P</i> < 0.001). Black patients with PNETs experience more vulnerable area-based social measures, a disparity which may be hidden when analyzing large geographic metrics.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e250029"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095900","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":"Octreotide infusion pump in patients with functional neuroendocrine tumors and refractory hormonal syndrome.","authors":"Kalyan Mansukhbhai Shekhda, Eleni Armeni, Dalvinder Mandair, Aspasia Manta, George Parker, Akanksha Sarma, Aimee Hayes, Martyn Caplin, Christos Toumpanakis","doi":"10.1530/EO-25-0016","DOIUrl":"10.1530/EO-25-0016","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate clinical outcomes, safety and survival measures of octreotide infusion pump (OIP) therapy in patients with metastatic neuroendocrine tumors (NETs) and refractory hormonal syndrome.</p><p><strong>Design: </strong>A retrospective analysis was conducted using data from patients treated with OIP therapy at a single center.</p><p><strong>Methods: </strong>Data on demographics, disease characteristics, biochemical profiles and treatment outcomes were extracted from electronic patient records.</p><p><strong>Results: </strong>Eighteen patients with NETs and debilitating symptoms refractory to maximum approved doses of somatostatin analogs (SSTAs) were included. The cohort comprised 18 patients (12 males (67%) and six females (33%)) with a median age of 64.5 years (IQR: 49.5-71). The most common tumor site was midgut (72.2%), followed by pancreas (22.2%). Refractory carcinoid syndrome was the primary indication for initiation of OIP therapy in 15 patients and VIPoma in three. Most tumors were WHO grade 1 or 2 (89%), and liver metastases were prevalent (94% of patients). At presentation, the median 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) level was 421.5 μmoL/24 h (<i>n</i>: 8). The mean starting OIP dose was 1,632 ± 522 μg/24 h, escalating to 2,166.7 ± 464 μg/24 h in 66.57% of patients. Symptomatic improvement was observed in 72% of patients, significantly reducing flushing and diarrhea. Patients who did not respond well to OIP therapy had more disease burden and had received more treatment lines before being started on OIP therapy.</p><p><strong>Conclusion: </strong>OIP therapy is an effective treatment option for symptom control in patients with refractory NET-related hormonal syndrome. Randomized controlled trials are warranted to confirm these findings and assess long-term outcomes.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e250016"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095897","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":"Emergency and routine presentation of neuroendocrine neoplasia in England: determinants of late presentation and survival outcomes.","authors":"Marie Line El Asmar, Mohamed Mortagy, Benjamin E White, Dan Burns, John Ramage","doi":"10.1530/EO-25-0012","DOIUrl":"https://doi.org/10.1530/EO-25-0012","url":null,"abstract":"<p><strong>Objective: </strong>The time from onset of symptoms of neuroendocrine neoplasia (NEN) to diagnosis ranges between 5 and 7 years. Risk factors associated with this and the difference in overall survival (OS) between routine and emergency presentation (RP and EP) are not known.</p><p><strong>Design: </strong>A retrospective, population-based study.</p><p><strong>Methods: </strong>A retrospective, population-based study of gastroenteropancreatic and lung NEN registered on England's national cancer between 2012 and 2021. Factors associated with worse OS, or emergency or late presentation (EP or LP), were evaluated using the Kaplan-Meier estimator, Cox and logistic regressions, and machine learning (ML) in two models.</p><p><strong>Results: </strong>A total of 21,345 NEN were included. 20.3% were EP. EP showed worse OS compared to RP. Factors associated with EP were male sex, advanced stage, worse deprivation and NEC. The ML model showed EP related to advanced stage, small intestinal NEN, NEC, advanced age, deprivation and male sex in decreasing order of importance. Factors associated with LP included EP, male sex and NEC. The ML model showed that NEC, small intestinal NEN, advanced age, EP and male sex are associated with LP in decreasing order of importance.</p><p><strong>Conclusion: </strong>EP is associated with poor survival. Addressing the associated factors may aid in timely diagnosis and improved survival.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e250012"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058401","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":"Clinical characteristics and prognosis of histological subtypes of papillary thyroid carcinoma in pediatric patients.","authors":"Junko Akaishi, Kiminori Sugino, Tetsuo Kondo, Wataru Kitagawa, Kenichi Matsuzu, Akifumi Suzuki, Chisato Tomoda, Ritsuko Okamura, Kiyomi Y Hames, Chie Masaki, Yoshiyuki Saito, Kana Yoshioka, Kosuke Inoue, Ryohei Katoh, Koichi Ito","doi":"10.1530/EO-24-0078","DOIUrl":"https://doi.org/10.1530/EO-24-0078","url":null,"abstract":"<p><p>The purpose of this study was to clarify the clinicopathological features and prognosis of histological subtypes of papillary thyroid carcinoma (PTC) in the pediatric population treated at a single institution. A total of 153 PTC patients ≤18 years of age who underwent initial surgery between 1979 and 2019 were investigated. There were 135 female and 18 male patients, with a mean age at the time of surgery of 16 (range, 8-18) years. The most common subtypes included classic PTC in 124 (81%), solid variant in 16 (10%), diffuse sclerosing variant in 7 (5%) and follicular variant in six (4%) according to the 5th edition of the WHO classification. At initial surgery, 49 patients (32%) had clinical lymph node metastases (cN1), 137 patients (90%) had pathological lymph node metastases (pN1), 73 patients (48%) had number of lymph node metastases (NLNMs) ≥10, 16 (10%) had gross extrathyroidal extension (ETE) and 18 (12%) had lung metastases. During a mean follow-up of 16 years, three (2%) patients died of their disease and 34 (25%) patients had recurrent disease. The 30-year cause-specific survival rate was 97.2%, and the 30-year disease-free survival (DFS) rate was 65.0%. On multivariate analysis, gross ETE, cN1 and NLNMs ≥10 identified as significant factors related to DFS (hazard ratio (HR) 4.13, confidence interval (CI) 1.48-9.96, <i>P</i> = 0.009; HR 2.34, CI 1.09-4.95, <i>P</i> = 0.0293; HR 2.81, CI 1.30-6.59, <i>P</i> = 0.008), but not histological subtype, were associated with disease recurrence. Histological subtypes were not associated with disease recurrence, but long-term follow-up of pediatric patients is necessary to investigate the biological characteristics.</p><p><strong>Synopsis: </strong>This retrospective study investigated the clinicopathological features and clinical outcomes of histological subtypes of PTC in a large series of pediatric patients treated at a single institution. It found that the prognosis of pediatric patients with PTC was excellent, but recurrence was common. In pediatric PTC, histological subtype did not affect survival and recurrence.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240078"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057965","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":"HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer.","authors":"Christiane Gruetzmacher, Bruna Sousa Pessoa, Flora Ladeira Craveiro, Marilena Nakaguma, Ericka Barbosa Trarbach, Rafael Loch Batista","doi":"10.1530/EO-24-0034","DOIUrl":"https://doi.org/10.1530/EO-24-0034","url":null,"abstract":"<p><strong>Purpose: </strong>Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), a member of the B7 family, is widely expressed across human cancers and is emerging as a promising immune checkpoint target for therapeutic development. This study aims to consolidate existing data on HHLA2 expression in endocrine-related cancers and evaluate its potential as a prognostic biomarker.</p><p><strong>Methods: </strong>Original studies published in English up to December 2024 were searched using PubMed, Web of Science and Embase databases. Search strategies combined MeSH terms and keywords related to 'HHLA2', 'B7-H7', 'B7y', 'B7-H5' and 'cancer', with a specific focus on endocrine-related cancers.</p><p><strong>Results: </strong>From a total of 117 studies reviewed, twelve met the inclusion criteria. Seven studies on pancreatic cancer indicated varied HHLA2 expression patterns, with high expression levels associated with better prognosis and improved overall survival. In ovarian cancer, one study suggested that high HHLA2 expression in tumor cells could predict improved survival. In contrast, another study linked HHLA2 to lymph node metastasis and poor overall survival, observing high expression only in stromal cells. On the other hand, studies on thyroid cancer and neuroendocrine tumors highlighted HHLA2's significance in disease progression, indicating poor prognosis and its association with metastasis.</p><p><strong>Conclusion: </strong>HHLA2 plays dual roles, exhibiting both immunosuppressive and tumor-suppressive functions in endocrine-related tumors, with its expression possibly influenced by the tumor microenvironment. This highlights its promise as an immune checkpoint biomarker and therapeutic target. The collective data from this review provide insights for future research endeavors in HHLA2-associated oncology.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240034"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047721","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":"Prospective cohort of pre-diagnosis hormone exposure and post-diagnosis sex hormone levels with survival outcomes: Alberta Endometrial Cancer Cohort Study.","authors":"Jamie L Benham, Renée L Kokts-Porietis, Jessica McNeil, Kerry S Courneya, Linda S Cook, Christine M Friedenreich","doi":"10.1530/EO-24-0066","DOIUrl":"10.1530/EO-24-0066","url":null,"abstract":"<p><strong>Purpose: </strong>To examine the associations between pre-diagnosis exogenous hormone exposure and endogenous sex hormone levels shortly after diagnosis with survival outcomes in endometrial cancer survivors.</p><p><strong>Methods: </strong>In this population-based cohort, females with endometrial cancer were followed from diagnosis to death or January 27, 2022. History of hormone exposure pre-diagnosis and sex-hormone levels shortly after diagnosis were obtained. The associations between hormone exposure and sex-hormone levels with disease-free survival (DFS) and overall survival (OS) were estimated using Cox proportional hazards regression by multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>During a median 16.9 years of follow-up (IQR = 15.5-18.1 years), 152 of the 540 participants had a recurrence and/or died. There were no statistically significant associations between exposure to hormonal contraception or menopausal hormone therapy before diagnosis and DFS or OS. Higher estrone levels post-diagnosis were associated with lower DFS (HR 1.56, 95% CI 1.04-2.34) and lower OS (HR 1.76, 95% CI 1.15-2.72). Lower DFS was also observed with higher estradiol levels (HR 1.56, 95% CI 1.02-2.41).</p><p><strong>Conclusion: </strong>There were no associations between pre-diagnosis hormonal contraception or menopausal hormone therapy use and endometrial cancer survival in our study. Endometrial cancer survivors with higher estrogen levels shortly after diagnosis had lower DFS and OS. Further research is needed to confirm these findings.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240066"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733485","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":"Oral cancer cells secrete stress neurotransmitter and proliferate in response to tobacco carcinogen NNK.","authors":"Flávia Alves Verza, Ana Lívia Santos-Sousa, Sandra Helena Penha Oliveira, Daniel Galera Bernabé","doi":"10.1530/EO-24-0076","DOIUrl":"10.1530/EO-24-0076","url":null,"abstract":"<p><strong>Purpose: </strong>Although there is a growing body of evidence showing the effects of stress-related catecholamines on oral cancer progression, to date there are no studies that have investigated whether oral squamous cell carcinoma (OSCC) cells can produce these hormones and whether this phenomenon is modulated by tobacco-related nitrosamines.</p><p><strong>Methods: </strong>In this study, we investigated whether keratinocytes (HaCaT) and OSCC-derived cell lines (SSC9 and SCC25) can secrete the neurotransmitter norepinephrine, as well as the effects of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on norepinephrine secretion and OSCC proliferation.</p><p><strong>Results: </strong>Supernatant from the HaCaT, SCC9 and SCC25 cells showed higher norepinephrine levels (6-, 14.9- and 15.1-fold higher, respectively) compared to the culture medium without cells. When the cells were stimulated with NNK, a tobacco-specific carcinogen, there was an increase in the levels of norepinephrine secretion by HaCaT and SCC25 cells but not by SCC9 cells. NNK (10 μM) induced cell proliferation in the HaCaT, SCC9 and SCC25 cell lines, and these effects were totally inhibited by blocking β-adrenergic receptors with propranolol. The NNK-induced OSCC cell proliferation was furthermore dependent on the activation of nicotinic acetylcholine receptors α4 (nAChR-α4) (completely in SCC9 cells and partially in SCC25 cells) but not on the activation of nAChR-α7. Inhibition of the β-adrenergic receptors, nAChR-α4 and nAChR-α7 did not block NNK-induced HaCaT proliferation.</p><p><strong>Conclusion: </strong>Our findings suggest that oral cancer cells secrete the neurotransmitter norepinephrine and that the tobacco nitrosamine NNK promotes increased cell proliferation through a stress-related cellular adrenergic pathway.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240076"},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626898","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":"Overview of management and therapeutic advances in medullary thyroid cancer.","authors":"Mark A Jara, Luciana Audi Castroneves","doi":"10.1530/EO-24-0077","DOIUrl":"10.1530/EO-24-0077","url":null,"abstract":"<p><p>Medullary thyroid carcinoma (MTC) is a rare cancer of the thyroid's calcitonin-producing C cells. This review covers recent advances in MTC treatment, emphasizing surgical and systemic therapies. For localized MTC, surgery remains the primary and most effective treatment, with total thyroidectomy and lymph node dissection providing the highest potential for cure. However, prognosis worsens significantly with local and distant metastases, underscoring the importance of early diagnosis and intervention. MTC can be sporadic or hereditary, with the latter associated with germline <i>RET</i> proto-oncogene mutations linked to multiple endocrine neoplasia types 2A and 2B. Genetic discoveries have enabled preventive measures such as prophylactic thyroidectomy, increasing the cure rate of hereditary cases. Since 2011, systemic treatment options have expanded with multikinase inhibitors (MKIs), such as vandetanib and cabozantinib, and selective RET inhibitors such as selpercatinib and pralsetinib. MKIs extend progression-free survival in advanced cases by targeting tumor growth and angiogenesis but can cause off-target effects. RET inhibitors offer precision treatment for <i>RET</i>-mutated tumors, showing high efficacy and fewer side effects, though resistance to these inhibitors has emerged, and current research focuses on developing next-generation inhibitors to overcome these barriers. Effective MTC management, particularly given its rarity, benefits from specialized high-volume centers. Precision medicine, standardized therapy selection and ongoing research are essential for improving outcomes in both <i>RET</i>-positive and <i>RET</i>-negative MTC patients.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240077"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626903","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}