Endocrine oncology (Bristol, England)最新文献

{"title":"Aripiprazole use as a cause of dopamine agonist failure in the treatment of prolactinomas.","authors":"Edward Mignone, Alistair K Jukes, Rowan Valentine, Richard Allison, Sunita M C De Sousa","doi":"10.1530/EO-24-0065","DOIUrl":"10.1530/EO-24-0065","url":null,"abstract":"<p><p>Prolactinomas are the most common hypersecretory pituitary adenoma. The traditional first-line therapy is dopamine agonists (DAs), which are highly effective and tolerated in the majority of cases. However, DAs have the potential for psychiatric complications, such as psychosis, impulse control disorders and anxiety/depression. It has been repeatedly suggested that aripiprazole may be considered in individuals with a psychiatric disorder and prolactinoma, potentially enabling DA dose reduction or even cessation. We report the first case of aripiprazole competing with cabergoline and reducing its efficacy in the treatment of a giant prolactinoma, as evidenced by an immediate and marked rise in serum prolactin (approximately 350% increase over 5 weeks) despite stable cabergoline dosing. We also present a systematic review of aripiprazole use in prolactinomas, showing that aripiprazole monotherapy effectively reduces serum prolactin and concurrently commenced aripiprazole/DA dual therapy may still permit prolactin lowering, although there were no previous cases where aripiprazole was added to an established DA therapy to indicate the direct effect of aripiprazole on DA efficacy. Based on our case, we support close monitoring of individuals with prolactinomas on dual aripiprazole/DA therapy and recommend against the addition of aripiprazole to DA therapy where timely prolactinoma treatment is essential (e.g. aggressive prolactinomas and those associated with compressive effects).</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240065"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191400","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":"A rare case of bladder paraganglioma treated successfully with robotic partial cystectomy.","authors":"Kalyan M Shekhda, Jessal M Palan, Christo B Albor, Simon Wan, Teng-Teng Chung","doi":"10.1530/EO-24-0044","DOIUrl":"10.1530/EO-24-0044","url":null,"abstract":"<p><p>Bladder paragangliomas are rare extra-adrenal urological tumors that account for around 0.05% of bladder cancers. Their diagnosis is often delayed because of the rarity of these tumors. There is a risk of an intraoperative hypertensive crisis if not diagnosed or identified before surgical removal. We describe a case of a 36-year-old lady presented with a 10-year history of post-micturition palpitations and headaches. Her biochemical workup showed raised urinary normetanephrine levels and imaging showed a ¹²³I MIBG-avid bladder mass compatible with bladder paraganglioma, although interestingly almost no tracer was picked up in ⁶⁸Ga DOTATATE imaging. She was started on phenoxybenzamine to control her blood pressure prior to surgery. She underwent a successful robotic partial cystectomy with no complications. After surgery, she remained symptom-free. Bladder paragangliomas are rare neuroendocrine tumors of the bladder, which need to be diagnosed and managed effectively to avoid intraoperative and long-term complications.</p><p><strong>Learning points: </strong>It is important for patients with a bladder lesion to have a comprehensive differential assessment and biochemical and radiological investigations including functional imaging.Multiple imaging modalities along with what is available are useful in the assessment of bladder paraganglioma.The key role of the multidisciplinary team is to plan treatment in the perioperative period for minimizing risk, especially in situations where optimal management is actively debated.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240044"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985510","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":"Expression of MMP-2, MMP-9 and TIMP-2 in pituitary tumors and their relationship with cavernous sinus invasion.","authors":"Ane Caroline Thé B Freire, Raquel S Jallad, Rafael L Batista, Andrea Glezer, Marcio C Machado, Gilberto Ochman, Valter A Cescato, Malebranche Berardo Carneiro Cunha Neto, Fernando P Frassetto, Raphael S S de Medeiros, Ericka B Trarbach","doi":"10.1530/EO-24-0037","DOIUrl":"10.1530/EO-24-0037","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in pituitary tumors and investigate their correlation with circulating plasma proteins and cavernous sinus invasion. In addition, the Ki-67 index was also assessed.</p><p><strong>Methods: </strong>Seventy-four patients (37 females) with pituitary adenomas were included, with preoperative peripheral blood collected in 29 cases. Tumor samples were evaluated for MMP-2, MMP-9, TIMP-2 and Ki-67 expression by immunohistochemistry. Protein plasma was semi-quantitatively detected using a commercial membrane antibody array.</p><p><strong>Results: </strong>Sixteen patients presented tumors invading the cavernous sinus. MMP-2 and TIMP-2 were slightly increased in these tumors compared to the noninvasive group, but the difference was not statistically significant. MMP-9 and TIMP-2 plasma concentrations did not correlate with tumor protein expression and also did not differ between the two groups. MMP-2 was not detected in plasma in any case. No statistically significant difference was observed when different tumor subtypes were considered. A significant difference was observed in tumor size (3.4 cm (2.8-4.9) vs 1.9 cm (1.3-2.6); <i>P</i> < 0.001) and in the Ki-67 index (1.8% (0.3-2.5) vs 0.5% (0.2-1.0); <i>P</i> = 0.01) between the invasive and noninvasive groups.</p><p><strong>Conclusions: </strong>In this cohort, we found no significant correlation between tissue and plasma levels of MMP-2, MMP-9 and TIMP-2 and cavernous sinus invasion in pituitary tumors. Further investigation is needed to elucidate the potential role of these markers in the invasiveness of pituitary tumors.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240037"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985517","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":"Treatment with BRAF/MEK: inhibitors in mutant BRAF V600E papillary craniopharyngioma.","authors":"Eva Marie Erfurth, Peter Siesjö, Pia C Sundgren, Björn Hammar, Sara Kinhult","doi":"10.1530/EO-24-0024","DOIUrl":"10.1530/EO-24-0024","url":null,"abstract":"<p><strong>Summary: </strong>Craniopharyngiomas (CPs) are rare brain epithelial tumours arising in the suprasellar region, infiltrating adjacent areas causing visual loss, panhypopituitarism, cognitive deficits and morbid obesity. Papillary CPs (PCPs) harbour in 94% BRAF mutation cases. Two patients with PCP and BRAF V600E mutations but with different tumour status were treated with BRAF and MEK inhibitors. Case I was diagnosed with biopsy and treated for 16 months with BRAF and MEK inhibitors. After 3.5 months, there was a 50% reduction of the tumour volume, and after 13 months, the tumour volume decreased from 2220 to 90 mm³ (96%). Two months after stopping the drugs, he was treated with fractionated cranial irradiation (54 Gy). No recurrence of the PCP was recorded. Eight months after stopping the drugs, he was diagnosed with an adenocarcinoma of the oesophagus, which led to his death 12 months later. In case II, a woman had had four surgeries due to recurrences of a PCP, and a BRAF V600E mutation was confirmed. After a new recurrence measuring 14 × 12 × 18 mm, she was started on BRAF and MEK inhibitors. After 4 months of treatment, a significant decrease to 8 × 9 × 13 mm was recorded. The treatment continued for 31 months, and the MRI demonstrated a stable unchanged size including scar tissue, with a volume reduction from 633 to 483 mm³. During treatment, her visual acuity improved in her left eye from 0.05 to 0.3. After stopping the drugs, 'watchful waiting' with repeated MRI was decided. She is now off treatment for 25 months, without any recurrence on MRI.</p><p><strong>Learning points: </strong>CPs are rare primary brain epithelial tumours arising in the suprasellar region from remnants of Rathke's pouch.CPs infiltrate adjacent areas causing visual loss, panhypopituitarism, cognitive deficits and morbid obesity.PCPs harbour in >90% BRAF V600E mutation.BRAF V600E mutation can successfully be treated with the combination of BRAF V600E and Mekinist inhibitors.It is suggested that PCP patients harbouring BRAF V600E mutation should be offered BRAF V600E and Mekinist inhibitors.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240024"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017446","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":"NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.","authors":"Po Hien Ear, Ilaria Marinoni, Talya Dayton, Rachael Guenter, Dawn E Quelle, Anna Battistella, Floryne O Buishand, Suganthi Chittaranjan, Yi-Cheih Nancy Du, Ines Marques, Natalia S Pellegata, Samira M Sadowski, Amit Tirosh, Simon April-Monn, Cinzia Aurilia, Renata Jaskula-Sztul, Maria Jesús Baena Moreno, Simone Donati, Katherine A English, Maria Almudena Hernandez Llorens, Harry Hodgetts, Francesca Marini, Maria Martins, Gaia Palmini, Beatriz Soldevilla, Jörg Schrader, Rajesh V Thakker, Kate E Lines","doi":"10.1530/EO-24-0055","DOIUrl":"10.1530/EO-24-0055","url":null,"abstract":"<p><p>Current models for the study of neuroendocrine tumours (NETs) are severely limited. While <i>in vitro</i> (e.g. cell lines), <i>ex vivo</i> (e.g. organoids) and <i>in vivo</i> (e.g. mice) models all exist, each has limitations. To address these limitations and collectively identify strategies to move the NET models field forward, we held an inaugural NET models meeting, hosted by our founding group: Dr Lines (Oxford), Prof. Quelle (Iowa), Dr Dayton (Barcelona), Dr Ear (Iowa), Dr Marinoni (Bern) and Dr Guenter (Alabama). This two-day meeting in Oxford (UK) was organised and supported by Bioscientifica Ltd and was solely dedicated to the discussion of NET models. The meeting was attended by ∼30 international researchers (from the UK, EU, Israel, USA and Canada). Plenary talks were given by Prof. Thakker, who summarised NET research over the past few decades, and Dr Schrader, who described the process and pitfalls of generating new cell lines. Eight researchers also presented their work on topics ranging from human cell 3D bioprinting to zebrafish models and included novel ideas and improvements on current concepts. This was followed by an interactive workshop, where discussion topics included a summary of currently available NET models, limitations of these models, barriers to developing new models, and how we can address these issues going forward. This white paper summarises the key points raised in these discussions and the future aspirations of the NET Models Consortium. The next meeting will take place in Oxford (UK) in 2025; contact contact@netcancerfoundation.com for more information.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240055"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017444","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":"Everything you ever wanted to know about cancer stem cells in neuroendocrine neoplasms but were afraid to ask.","authors":"Ignacio Ruz-Caracuel, Sergio Pedraza-Arevalo, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Julie Earl, Bruno Sainz","doi":"10.1530/EO-24-0006","DOIUrl":"10.1530/EO-24-0006","url":null,"abstract":"<p><p>While the role of cancer stem cells (CSCs) in tumorigenesis, chemoresistance, metastasis, and relapse has been extensively studied in solid tumors, such as adenocarcinomas or sarcomas, the same cannot be said for neuroendocrine neoplasms (NENs). While lagging, CSCs have been described in numerous NENs, including gastrointestinal and pancreatic NENs (PanNENs), and they have been found to play critical roles in tumor initiation, progression, and treatment resistance. However, it seems that there is still skepticism regarding the role of CSCs in NENs, even in light of studies that support the CSC model in these tumors and the therapeutic benefits of targeting them. For example, in lung neuroendocrine carcinoids, a high percentage of CSCs have been found in atypical carcinoids, suggesting the presence of CSCs in these cancers. In PanNENs, CSCs marked by aldehyde dehydrogenases or CD90 have been identified, and targeting CSCs with inhibitors of molecular pathways has shown therapeutic potential. Overall, while evidence exists for the presence of CSCs in NENs, either the CSC field has neglected NENs or the NEN field has not fully embraced the CSC model. Both might apply and/or may be a consequence of the fact that NENs are a relatively rare and heterogeneous tumor entity, with confusing histology and nomenclature to match. Regardless, this review intends to summarize our current knowledge of CSCs in NENs and highlight the importance of understanding the role of CSCs in the biology of these rare tumors, with a special focus on developing targeted therapies to improve patients' outcomes.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240006"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017442","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":"Alternative splicing generates isoform diversity in <i>MEN1</i>.","authors":"Anassuya Ramachandran, Polona Le Quesne Stabej, Veronica Boyle, Marianne S Elston, Sharon Pattison, Ben Lawrence, Cris Print","doi":"10.1530/EO-24-0014","DOIUrl":"10.1530/EO-24-0014","url":null,"abstract":"<p><p>Although the gene <i>MEN1</i> has a long-standing association with cancer, its mechanisms of action remain incompletely understood, acting both as a tumour suppressor in neuroendocrine tumours and as an oncogene in leukaemia. The best-characterised isoform of the encoded protein, MENIN, is the 610-amino acid MENIN isoform 2. We hypothesise that some of the complexity of <i>MEN1</i> biology can be attributed to a currently unappreciated contribution of different MENIN isoforms. Through <i>in silico</i> data mining, we show alternative splicing along the entire length of <i>MEN1</i>. Splice junction data suggest that the transcript encoding MENIN isoform 2 is the most abundant in all tissues examined, making a strong argument for this to be the reference transcript/protein isoform of <i>MEN1</i>. We also report novel splicing events, including a novel exon from within intron 7 that is relatively highly expressed in many tissues. These splicing events are predicted to contribute to MENIN diversity by generating isoforms with in-frame insertions, deletions or unique amino termini that, in turn, could have altered interactions with partner proteins. Finally, we have compiled 2574 unique genomic variants reported in <i>MEN1</i> within somatic and germline databases and have identified several variants that could impact individual MENIN isoforms. We have also collated studies pertinent to MENIN function in the literature and summarised the impact of <i>MEN1</i> variants on 74 biological variables. We propose a set of four <i>MEN1</i> variants, MENIN^L22R, MENIN^H139D, MENIN^A242V and MENIN^W436R, that represent a cohort with different biological properties, which should be investigated concurrently to better dissect MENIN function.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240014"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796671","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":"Predictors of hypocalcaemia and hypoparathyroidism in patients undergoing thyroidectomy for benign and malignant pathologies.","authors":"Jino Johns Lalitha, Natarajan Ramalingam, Remya Rajan, Jeyashanth Riju, Antony Abraham Paulose, Rajiv Charles Michael, Amit Jiwan Tirkey, Twisha Adhikari, Shalini Sahu, R Nagayazhini","doi":"10.1530/EO-24-0022","DOIUrl":"10.1530/EO-24-0022","url":null,"abstract":"<p><strong>Objective: </strong>To analyse the risk factors of hypoparathyroidism and hypocalcaemia after total thyroidectomy.</p><p><strong>Methods: </strong>Clinical data of patients who underwent total thyroidectomy at a tertiary care hospital in southern part of India were collected retrospectively from January 2021 to May 2023. Multivariate logistic regression was used to analyse the risk factors associated with transient hypoparathyroidism and hypocalcaemia separately.</p><p><strong>Results: </strong>A total of 300 patients who underwent total thyroidectomy were enroled. The median age of the study population was 41 years, and 70% were females. Histopathological examination showed that 80.3% had thyroid cancer. The incidence of postoperative transient hypoparathyroidism was 26.7%, while postoperative transient hypocalcaemia was 12.3%. Multivariate analysis showed that the presence of hypothyroidism before surgery (OR = 3.230, 95% CI: 1.368-7.624, <i>P</i> = 0.007), performing central compartment neck dissection (CCND) (OR = 2.196, 95% CI: 1.133-4.257, <i>P</i> = 0.02) and parathyroid gland in the surgical specimen (OR = 5.547, 95% CI: 3.065-10.036, <i>P</i> < 0.0001) were independent predictors of postoperative transient hypoparathyroidism. Female gender (OR = 2.689, 95% CI: 1.049-6.895, <i>P</i> = 0.039), presence of parathyroid in the surgical specimen (OR = 1.067, 95% CI: 0.367-8.438, <i>P</i> = 0.004) and performing CCND (OR = 2.192, 95% CI: 0.990-4.850, <i>P</i> = 0.05) were independent predictors of postoperative transient hypocalcaemia.</p><p><strong>Conclusion: </strong>Hypoparathyroidism and hypocalcaemia after thyroid surgery are common, and most of them are transient. The independent predictors of hypoparathyroidism and hypocalcaemia differ. Hypoparathyroidism appears to be a better predictor for patients who will develop postoperative hypocalcaemia.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240022"},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795873","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":"Time toxicity of lutetium 177 in gastroenteropancreatic neuroendocrine tumours.","authors":"Marcos Daniel Bortz, Andres Rodriguez, Maria Romina Luca, Federico Waisberg, Diego Enrico, Berenice Freile, Greta Catani, Federico Esteso, Martina Musumeci, Eliana Vazquez, Matías Chacón, Juan Manuel O'Connor, Silvina Racioppi","doi":"10.1530/EO-24-0028","DOIUrl":"10.1530/EO-24-0028","url":null,"abstract":"<p><strong>Objectives: </strong>We aim to investigate the time toxicity of patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate in a single institution.</p><p><strong>Design: </strong>This is a retrospective cohort study.</p><p><strong>Methods: </strong>All patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate at the Alexander Fleming Institute were included. Our primary endpoint was to evaluate time toxicity, which accounted for every day that the patient had contact with any department of any healthcare institution.</p><p><strong>Results: </strong>Our cohort included 21 patients with metastatic disease, female sex 86%, and a median age of 55 (IQR 44-63). The primary tumour site was the small intestine in 47.6% of the cases. The median number of previous systemic treatments for advanced disease was two (IQR 2-3). The overall response rate was 19%, and 66.6% had clinical benefit. The median calculated 'time toxicity' was 11 days (IQR 8-18), representing 5.7% of the total treatment duration. The main contributors to time toxicity included infusion days, blood draws, radiological scans, and hospitalisations (median of 4 days for each).</p><p><strong>Conclusion: </strong>Lutetium-177 Dotatate treatment for gastroenteropancreatic neuroendocrine tumours was associated with low time toxicity, excellent tolerability, a good response and prolonged PFS, of which the median was not reached in the short follow-up we present. Newer treatments with different mechanisms of action provide longer survival and widen the landscape of choices. Understanding new clinical endpoints is important for the transition into a more modern clinical practice, strengthening personalised and patient-oriented strategies.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240028"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796263","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":"Multifaceted modeling of small intestinal neuroendocrine tumors.","authors":"Stephen Gabriel Andrews, Steven D Forsythe, James P Madigan, Samira Mercedes Sadowski","doi":"10.1530/EO-24-0038","DOIUrl":"10.1530/EO-24-0038","url":null,"abstract":"<p><p>Small intestinal neuroendocrine tumors, siNETs, are a group of rare cancers that arise from neuroendocrine cells in the lining of the jejunum and ileum, which are either classified as tumors, siNETs, or small intestinal neuroendocrine carcinomas, siNECs. Current treatment strategies for low-grade tumors include surgical resection, peptide radionucleotide receptor therapy, and somatostatin analogues, while high-grade and recurrent tumors may receive cytotoxic chemotherapy. These limited treatment options are linked to the lack of representative models that can both reflect the biology of the tumor and are amenable to mid-to-high throughput experimentation. Cell line generation is challenging considering the indolent nature of primary lesions, although some attempts have been successful using a variety of methods and include the primary P-STS line and those derived from metastatic lesions, including GOT1, CNDT2.5, and HC45. Patient-derived modeling, including organoids and xenografting, have allowed for multicellular and 3D representations of the original tumor. These specific models allow for multicellular populations derived from the tumor, providing better tumor representation for use in drug screening and <i>in vitro</i> assays. Currently, there are limited, although increasing, published models of siNETs implanted as xenografts in mice and zebrafish. As these cellular and animal models provide insights into siNET biology, theragnostic modeling has provided key information on the clinical progression and treatment of this disease. Significant strides toward more representative models have been made throughout the last decade. In this review, details of these attempts as well as future directions and strategies for more robust models will be addressed.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240038"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795683","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}