Endocrine-related cancer最新文献

Impact of treatment on quality of life in neuroendocrine neoplasms survivors. 治疗对神经内分泌肿瘤幸存者生活质量的影响。

Endocrine-related cancer Pub Date : 2025-07-15 DOI: 10.1530/ERC-24-0303

Roberta Modica, Elio Benevento, Anna La Salvia, Rossella Mazzilli, Carla Pandozzi, Giulia Pecora, Luigi Barrea, Annamaria Colao, Antongiulio Faggiano

{"title":"Impact of treatment on quality of life in neuroendocrine neoplasms survivors.","authors":"Roberta Modica, Elio Benevento, Anna La Salvia, Rossella Mazzilli, Carla Pandozzi, Giulia Pecora, Luigi Barrea, Annamaria Colao, Antongiulio Faggiano","doi":"10.1530/ERC-24-0303","DOIUrl":"https://doi.org/10.1530/ERC-24-0303","url":null,"abstract":"Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumors, ranging from well-differentiated, slow-growing neuroendocrine tumor (NET) with long-term survival, to aggressive high-grade neuroendocrine carcinoma (NEC). Advances in treatment and earlier diagnosis have led to improved survival outcomes; however, data regarding patients' quality of life (QoL) during therapy and in the post-treatment phase remain limited. This narrative review aims to analyze available data on QoL in NEN patients undergoing medical therapies including nutritional considerations, to improve and personalize therapeutic strategies. A literature research was performed using online databases, including MEDLINE (via PubMed), and Scopus employing multiple keywords combinations up to October 2024. Somatostatin analogues (SSA) and radioligand therapy (RLT) have demonstrated good tolerability profiles and efficacy on QoL, especially in patients with carcinoid syndrome, impacting on both physical and emotional domains. On the contrary, multikinase inhibitors have been associated with declines in general health status and sexual and physical functioning. Data on chemotherapy are conflicting, with some evidence suggesting a favorable QoL profile due to tumor control. Interestingly, approximately 30% of NEN survivors report persistence of symptoms related to depression. Both treatment-related side effects and disease-related symptoms may impact QoL, affecting nutritional status, that should be carefully considered. Despite standardized QoL assessments are lacking in nutritional studies, adherence to Mediterranean diet seems to positively influence symptom burden in NEN patients. In conclusion, evidence supports that SSA and RLT contribute to improve QoL, likely due to symptom control. Further research is needed to better characterize the QoL impact of other therapies using standardized assessment tools, in order to optimize therapeutic management.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639020","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

Epigenetic Therapeutics: Reprogramming Triple-Negative Breast Cancer into Responsive Subtypes. 表观遗传疗法：将三阴性乳腺癌重编程为响应亚型。

Endocrine-related cancer Pub Date : 2025-07-11 DOI: 10.1530/ERC-25-0125

Wafaa S Ramadan, Aya Mudhafar Al-Azawi, Lama Lozon, Rawan R Kawaf, Ragheb Alsheikh Zein, Yahia El-Gharib, Raafat El-Awady

{"title":"Epigenetic Therapeutics: Reprogramming Triple-Negative Breast Cancer into Responsive Subtypes.","authors":"Wafaa S Ramadan, Aya Mudhafar Al-Azawi, Lama Lozon, Rawan R Kawaf, Ragheb Alsheikh Zein, Yahia El-Gharib, Raafat El-Awady","doi":"10.1530/ERC-25-0125","DOIUrl":"10.1530/ERC-25-0125","url":null,"abstract":"Triple negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging subtypes of BC due to its lack of targeted treatment options and high plasticity. Increasing evidence suggests that epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA regulation, play a pivotal role in facilitating TNBC phenotype by influencing the expression of genes involved in subtype reprogramming. Modulating these epigenetic marks offers a promising strategy to drive TNBC subtype conversion toward less aggressive forms that are more responsive to treatment, thereby enhancing therapeutic efficacy. By targeting enzymes such as DNA methyltransferases and histone modifiers using epigenetic drugs (epidrugs), TNBC cells can be re-sensitized to hormone therapy, chemotherapy, and targeted treatments. This review delves into the role of epigenetic modulation in harnessing the plasticity of TNBC to drive its conversion into subtypes with better prognoses and discusses problems and limitations associated with the use of epidrugs in this context. By promoting subtype conversion, epidrugs offer a promising strategy for providing more personalized and effective therapies for TNBC patients.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602633","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

Next-generation sequencing of targetable gene fusions in radioiodine-refractory thyroid cancer: a multicenter study. 放射性碘难治性甲状腺癌中靶向基因融合的新一代测序：一项多中心研究。

Endocrine-related cancer Pub Date : 2025-07-07 Print Date: 2025-07-01 DOI: 10.1530/ERC-25-0089

Jungmin Yoo, Mijin Kim, Hee Kyung Kim, Dong Yeob Shin, Min Ji Jeon, Bo Hyun Kim, Ho-Cheol Kang, Jaekyung Lee, Dong-Jun Lim, Won Gu Kim

{"title":"Next-generation sequencing of targetable gene fusions in radioiodine-refractory thyroid cancer: a multicenter study.","authors":"Jungmin Yoo, Mijin Kim, Hee Kyung Kim, Dong Yeob Shin, Min Ji Jeon, Bo Hyun Kim, Ho-Cheol Kang, Jaekyung Lee, Dong-Jun Lim, Won Gu Kim","doi":"10.1530/ERC-25-0089","DOIUrl":"10.1530/ERC-25-0089","url":null,"abstract":"We aimed to determine the prevalence and clinical significance of targetable gene fusions in patients with radioiodine-refractory thyroid cancer. This multicenter retrospective cohort study enrolled 111 patients from five tertiary medical centers, with molecular profiling performed using targeted next-generation sequencing. The analysis revealed that 58 (52.3%) patients possessed BRAFV600E mutation, while 25 (22.5%) had RAS mutations. Among the 20 (18.0%) patients with gene fusions, 13 had RET fusions, three had NTRK fusions, one had a BRAF fusion, and three had nondriver gene fusions. The group with targetable gene fusions was significantly younger compared to those with BRAF or RAS mutations (P < 0.001) and predominantly had classic papillary thyroid carcinoma. Furthermore, targetable gene fusions were detected in 30.8% of patients with refractory thyroid cancer harboring wild-type BRAF. More than half of the patients received systemic tyrosine kinase inhibitor therapy and three patients with confirmed RET or NTRK fusions achieved meaningful clinical benefit with selective agents. These findings suggest that a stepwise molecular testing strategy - initiating with BRAF single gene analysis followed by next-generation sequencing for assessing targetable gene fusions - may be a rational approach, particularly for younger patients with papillary thyroid carcinoma, for identifying candidates for precision therapy. This supports the integration of molecular profiling into routine clinical practice for radioiodine-refractory thyroid cancer and emphasizes its utility in guiding personalized treatment decisions in this challenging disease subset.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499914","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

Clinical Features of Plurihormonal Pituitary Adenoma Subtypes. 多激素垂体腺瘤亚型的临床特征。

Endocrine-related cancer Pub Date : 2025-07-07 DOI: 10.1530/ERC-25-0020

Christie G Turin, Katja Kiseljak-Vassiliades, Margaret E Wierman, Kevin Lillehei, B K Kleinschmidt-DeMasters

{"title":"Clinical Features of Plurihormonal Pituitary Adenoma Subtypes.","authors":"Christie G Turin, Katja Kiseljak-Vassiliades, Margaret E Wierman, Kevin Lillehei, B K Kleinschmidt-DeMasters","doi":"10.1530/ERC-25-0020","DOIUrl":"10.1530/ERC-25-0020","url":null,"abstract":"Plurihormonal pituitary neuroendocrine tumors/pituitary adenomas (PitNET/PAs) express multiple hormones and/or transcription factors. The two most common subtypes within the plurihormonal category are immature PIT-1 (pituitary-specific POU-class homeodomain factor-1) lineage tumors and mature PIT-1 plurihormonal tumors, most of which show PIT-1/SF-1 (steroidogenic factor 1) co-expression. Our aim is to provide direct comparison between these two PIT-1 plurihormonal tumor types in terms of demographic, radiological, neurosurgical, and endocrinological features. A database search and chart review of patients with plurihormonal PitNET/PAs who underwent resection between 2018 and 2024 was performed. Twenty-six plurihormonal PitNET/PAs (12 immature PIT-1-lineage, 14 mature PIT-1/SF-1 co-expressors) were identified. Immature PIT-1 lineage tumors were larger than mature PIT-1/SF-1 co-expressors (median size 27.5 mm vs 16 mm, p=0.02). No significant differences were detected between the two groups in terms of gender (females 67% vs. 50%), median age (45 vs 50 years), hormonal activity (83% vs 79%), invasion of the cavernous sinuses (50% each), residual tumor after surgery (55% vs 43%) or rate of recurrence (9% vs 7%), respectively. Immature PIT-1 lineage tumors trended towards higher Ki-67 levels when compared to mature PIT-1/SF-1 co-expressors (30% vs 0%, p=0.21) as well as need for medical therapy after surgery for hormone excess (33% vs 7%, p=0.15) but this was not statistically significant. In conclusion, immature PIT-1 lineage tumors exhibit larger size and an increased requirement for postoperative medical therapy than mature PIT-1/SF-1 co-expressors, underscoring the usefulness of careful histologic analysis. In contrast, these two plurihormonal subtypes cannot be predicted pre-operatively by gender, age, or hormonal profile.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562409","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

Improved and individualized approach to adrenal surgery. 改进的个体化肾上腺手术方法。

Endocrine-related cancer Pub Date : 2025-07-07 Print Date: 2025-07-01 DOI: 10.1530/ERC-24-0296

Tobias Carling, Meredith LaRue

{"title":"Improved and individualized approach to adrenal surgery.","authors":"Tobias Carling, Meredith LaRue","doi":"10.1530/ERC-24-0296","DOIUrl":"10.1530/ERC-24-0296","url":null,"abstract":"Adrenal surgery has undergone significant advancements, driven by technological innovations, enhanced surgical techniques, and a deeper understanding of adrenal gland pathophysiology. This review highlights the transition toward modern, individualized adrenal surgery, emphasizing minimally invasive techniques, precision medicine, and the development of specialized centers performing more than 500 adrenalectomies a year. Minimally invasive adrenalectomy, specifically the mini back scope adrenalectomy (MBSA, also known as posterior retroperitoneoscopic adrenalectomy), has become the standard of care for most adrenal pathologies, enabling precise function-preserving (partial) adrenalectomy, and offering reduced morbidity, shorter hospital stays, and faster recovery compared to open and transabdominal surgery, whether robotic or laparoscopic. Molecular pathology and enhanced imaging modalities have improved preoperative planning and intraoperative decision-making, allowing for precise tumor localization and preservation of adrenal function. Molecular profiling of adrenal tumors has provided insights into tumor behavior, enabling tailored surgical approaches. In addition, multidisciplinary collaboration has been crucial in developing comprehensive treatment strategies, particularly for complex cases such as familial pheochromocytomas, equivocal unilateral and bilateral primary hyperaldosteronism, and ACTH-independent adrenal hypercortisolism due to bilateral adrenal lesions, adrenocortical carcinoma, and metastatic adrenal disease. Patient-specific factors, including genetic predispositions and comorbidities, are increasingly considered to optimize surgical outcomes and personalize postoperative care. As we enter this improved and individualized era of adrenal surgery, ongoing research and technological advancements are expected to continue to enhance patient outcomes and expand the indications for adrenal surgery.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478328","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

Plasma metabolomics for the preoperative diagnosis of parathyroid carcinoma. 血浆代谢组学在甲状旁腺癌术前诊断中的应用。

Endocrine-related cancer Pub Date : 2025-07-01 DOI: 10.1530/ERC-24-0192

Jinheng Xiao, Ming Cui, Qingyuan Zheng, Sen Yang, Tianqi Chen, Ya Hu

{"title":"Plasma metabolomics for the preoperative diagnosis of parathyroid carcinoma.","authors":"Jinheng Xiao, Ming Cui, Qingyuan Zheng, Sen Yang, Tianqi Chen, Ya Hu","doi":"10.1530/ERC-24-0192","DOIUrl":"10.1530/ERC-24-0192","url":null,"abstract":"Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. Preoperative diagnosis remains a major challenge in clinical practice because of limited diagnostic methods and non-specific clinical features. This study aimed to describe the distinct plasma metabolic profiles of PC and parathyroid adenoma (PA) patients and identify promising biomarkers for the preoperative differential diagnosis of PC. A total of 115 patients were enrolled in this retrospective study, including 70 patients (24 PC and 46 PA) in the discovery cohort and 45 patients (15 PC and 30 PA) in the validation cohort. Plasma samples were collected before operation. LC-MS/MS analysis was utilised on the discovery cohort to explore the metabolic profile and find out differentially abundant metabolites. Subsequently, potential diagnostic biomarkers were verified in an external validation cohort to find out novel biomarkers for the differential diagnosis of PC before surgery. Compared with the plasma samples of PA patients, a total of three upregulated and 42 downregulated metabolites were identified by MS/MS in the plasma samples of PC patients. The differentially abundant metabolites were significantly enriched in the arachidonic acid, tryptophan, and hormone metabolism pathways. Notably, 7-ketodeoxycholic acid (P = 0.002, AUC = 0.804) and tryptophan (P < 0.001, AUC = 0.838) were confirmed to show high accuracy in differential diagnosis in the validation cohort. Therefore, metabolomics analysis of parathyroid neoplasms revealed significant differences in metabolic profiles between PAs and PCs. The plasma levels of 7-ketodeoxycholic acid and tryptophan could serve as potential diagnostic biomarkers for PC.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319013","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

Identification of protein-coding genes associated with metastatic prostate cancer. 转移性前列腺癌相关蛋白编码基因的鉴定。

Endocrine-related cancer Pub Date : 2025-06-26 Print Date: 2025-07-01 DOI: 10.1530/ERC-25-0070

Mina Sattari, Hanna Rauhala, Leena Latonen, William B Isaacs, Matti Nykter, G Steven Bova, Juha Kesseli, Tapio Visakorpi

{"title":"Identification of protein-coding genes associated with metastatic prostate cancer.","authors":"Mina Sattari, Hanna Rauhala, Leena Latonen, William B Isaacs, Matti Nykter, G Steven Bova, Juha Kesseli, Tapio Visakorpi","doi":"10.1530/ERC-25-0070","DOIUrl":"10.1530/ERC-25-0070","url":null,"abstract":"Prostate cancer (PCa) is a significant cause of male mortality worldwide. Since metastases are the underlying cause of lethality, identifying markers for metastatic potential would be highly valuable. To address this issue, we set out to identify protein-coding genes with metastasis-specific expression changes in PCa. We employed a previously reported unique cohort consisting of metastases from castration-resistant prostate cancer (mCRPC) and matching primary tumors. Our comprehensive gene expression analyses identified 85 differentially expressed genes (DEGs) associated specifically with mCRPC, comprising 63 upregulated and 22 downregulated genes. Investigation of the transcription factors (TFs), such as the androgen receptor and its co-regulators FOXA1 and HOXB13, known to be important in prostate tumorigenesis, revealed their involvement in the differential expression of these genes. Furthermore, we identified enriched binding sites for nine TFs, namely EZH2, SUZ12, TLE3, TP63, CBX7, RNF2, SP140, JARID2, and CBX8, in the regulatory regions of the DEGs. Analysis of progression-free survival of prostatectomy-treated men highlighted 16 DEGs with significant prognostic value. Of these, three genes (FRMPD1, TMEM18, and ZNHIT3) were independent prognostic markers of biochemical recurrence. TMEM18 has putative androgen receptor-binding sites in its promoter region, and analysis of LNCaP cells following stimulation with dihydrotestosterone revealed a significant upregulation of TMEM18, confirming the androgen regulation of the gene. Furthermore, we confirmed the prognostic significance of TMEM18 expression at the protein level with immunohistochemistry (IHC) in a primary PCa tumor cohort. In conclusion, we identified 85 mCRPC-associated genes and showed that TMEM18 has prognostic value in early PCa.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319012","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

Predictors of cancer in patients with endogenous Cushing's syndrome. 内源性库欣综合征患者癌症的预测因素。

Endocrine-related cancer Pub Date : 2025-06-24 Print Date: 2025-07-01 DOI: 10.1530/ERC-25-0059

Yaron Rudman, Genady Drozdinsky, Hiba Masri-Iraqi, Tzippy Shochat, Shiri Kushnir, Ilan Shimon, Maria Fleseriu, Amit Akirov

{"title":"Predictors of cancer in patients with endogenous Cushing's syndrome.","authors":"Yaron Rudman, Genady Drozdinsky, Hiba Masri-Iraqi, Tzippy Shochat, Shiri Kushnir, Ilan Shimon, Maria Fleseriu, Amit Akirov","doi":"10.1530/ERC-25-0059","DOIUrl":"10.1530/ERC-25-0059","url":null,"abstract":"We previously reported an increase in overall cancer risk in patients with endogenous Cushing's syndrome (CS), mainly during the 10-year period following CS diagnosis. To identify predictors of cancer in patients with CS, we conducted this retrospective nationwide cohort study of patients with CS, diagnosed between 2000 and 2023 in Israel. The cohort comprised 609 patients with CS (age at diagnosis, 48.1 ± 17.2 years; 65.0% women) and 3,018 age-, sex-, socioeconomic status-, and body mass index-matched controls (1:5 ratio). Patients were grouped according to the occurrence of any malignancy within 10-years after the diagnosis of CS. Cox proportional hazards models, with death as a competing event, were used to identify predictors of cancer development. Independent predictors of cancer development in patients with CS included age ≥60 years (HR 1.75, 95% CI 1.01-2.68), male gender (HR 1.67, 95% CI 1.04-3.05), and adrenal-origin CS (HR 1.66, 95% CI 1.01-2.73). Baseline urinary-free cortisol levels were not associated with cancer development. Patients with ≥4 CS-associated comorbidities had a higher cancer risk (HR 1.76, 95% CI 1.03-3.02; age- and sex-adjusted). The overall 10-year risk of malignancy was twice as high in patients with CS compared to matched controls, with cancer developing, on average, 5 years earlier in patients with CS (62.3 ± 15.0 vs 67.2 ± 12.3 years). Cancer-related mortality at 10-years was twice as high in deceased patients with CS, compared to deceased controls. In conclusion, age ≥60 years at CS diagnosis, male gender, and adrenal-origin CS are independent predictors of cancer diagnosis within 10-years of initial confirmation of CS.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251503","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

Targeting anti-apoptosis as a therapeutic strategy in neuroendocrine neoplasms. 靶向抗细胞凋亡作为神经内分泌肿瘤的治疗策略。

Endocrine-related cancer Pub Date : 2025-06-21 Print Date: 2025-07-01 DOI: 10.1530/ERC-24-0341

Vineeth Sukrithan, Uzair Ahmed, Harris Krause, Nishant Gandhi, Andrew Elliott, Andrew Hinton, Phillip Walker, Ari Vanderwalde, Ye Zhou, Dipen C Patel, Emil Lou, Heloisa P Soares, Kerry A Rogers, Bhavana Konda

{"title":"Targeting anti-apoptosis as a therapeutic strategy in neuroendocrine neoplasms.","authors":"Vineeth Sukrithan, Uzair Ahmed, Harris Krause, Nishant Gandhi, Andrew Elliott, Andrew Hinton, Phillip Walker, Ari Vanderwalde, Ye Zhou, Dipen C Patel, Emil Lou, Heloisa P Soares, Kerry A Rogers, Bhavana Konda","doi":"10.1530/ERC-24-0341","DOIUrl":"10.1530/ERC-24-0341","url":null,"abstract":"BCL-2 is an anti-apoptotic protein expressed by aggressive neuroendocrine neoplasms (NENs). We report a case of a patient with a pancreatic neuroendocrine tumor (pNET) who received venetoclax, a BCL-2-targeting drug for the treatment of chronic lymphocytic leukemia. We further characterized BCL2 expression in NENs from a large multi-institutional patient cohort. Clinical data were abstracted from the records of a patient with a pNET. Next-generation sequencing of DNA (592-gene panel or whole exome) and RNA (whole transcriptome) was performed on 636 NENs of pancreatic (P-NENs), small bowel (SB-NENs), colorectal (CR-NENs), and lung (L-NENs) origin by Caris Life Sciences. Comparisons were performed against site-matched non-NEN cancers. BCL2- or MKI67- high and low cohorts were defined based on the top and bottom quartiles of gene expression. The patient with a pNET who received venetoclax had a partial response in the primary tumor that lasted 30 months. CR-, L-, and P-NENs had significantly higher expression of BCL2 compared to non-NEN counterparts. BCL2 expression was significantly higher in MKI67-high tumors among all NEN subtypes. In P-NENs, there was a higher prevalence of RB1 mutations in BCL2-high vs BCL2-low (40 vs 4.9%, P < 0.005). Patients with BCL2-high P-NENs had significantly decreased overall survival (HR 1.94, 95% CI 1.0-3.76, P = 0.047). Immune checkpoint gene expression and T cells were enriched in BCL2-high tumors across all subtypes. In summary, we report the first known case of a pancreatic NET with response to venetoclax. BCL2 expression correlated with high MKI67 expression, worse survival, and a highly immune-enriched microenvironment.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287580","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

Challenges and opportunities in systems biology education. 系统生物学教育的挑战与机遇。

Endocrine-related cancer Pub Date : 2025-06-19 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0024

Jeff Didier, Sophia Croce, Salma Bayoumi, Elena Valceschini, Hugues Escoffier, Evelyn Gonzalez, Ali Kishk, Apurva Badkas, Sébastien De Landtsheer, Thomas Sauter

引用次数: 0