Endocrine-related cancer最新文献_第7页

Association of serum steroids with survival in metastatic hormone-sensitive prostate cancer. 血清类固醇与对激素敏感的转移性前列腺癌患者生存期的关系。

Endocrine-related cancer Pub Date : 2025-01-10 Print Date: 2025-02-01 DOI: 10.1530/ERC-24-0140

Elahe A Mostaghel, Victoria Wang, Brett T Marck, Nima Sharifi, Alvin M Matsumoto, Christopher J Sweeney

{"title":"Association of serum steroids with survival in metastatic hormone-sensitive prostate cancer.","authors":"Elahe A Mostaghel, Victoria Wang, Brett T Marck, Nima Sharifi, Alvin M Matsumoto, Christopher J Sweeney","doi":"10.1530/ERC-24-0140","DOIUrl":"10.1530/ERC-24-0140","url":null,"abstract":"The CHAARTED study showed that adding docetaxel (Doc) to androgen deprivation therapy (ADT) in men initiating treatment for metastatic hormone-sensitive prostate cancer (mHSPC) prolongs survival, particularly in high-volume disease. Androgens drive both mHSPC and metastatic castration-resistant prostate cancer (mCRPC). Lower nadir serum testosterone concentrations are associated with better outcomes in men treated with ADT for biochemical relapse, while higher androgens at mCRPC are associated with better prognosis and increased benefit from abiraterone. We evaluated the association of serum steroids at 24 weeks with overall survival (OS) and time to CRPC (TTCRPC) in 588 men with available samples from the CHAARTED study. Steroid concentrations were measured using mass spectrometry. The median testosterone concentration at 24 weeks was 8 ng/dL and did not differ in ADT alone vs ADT plus Doc arm. Achieving nadir testosterone below 20 ng/dL was not associated with OS or TTCRPC in either arm. In high-volume disease, Doc conferred an OS and TTCRPC benefit regardless of steroid concentrations. In low-volume disease, steroid concentrations in the lowest quartile at 24 weeks identified a subset of men with poor survival outcomes more like high-volume disease, and in whom Doc was also associated with improved OS and TTCRPC. The known OS benefit of Doc in high-volume mHSPC is not modified by serum steroid concentrations achieved on treatment. In low-volume disease, steroid concentrations in the lowest quartile may identify a poor prognosis subset in whom Doc also confers OS benefit.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718039","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

Mechanisms of resistance to RET-directed therapies. 对ret定向治疗的耐药机制。

Endocrine-related cancer Pub Date : 2025-01-10 Print Date: 2025-02-01 DOI: 10.1530/ERC-24-0224

Roderick J Clifton-Bligh

{"title":"Mechanisms of resistance to RET-directed therapies.","authors":"Roderick J Clifton-Bligh","doi":"10.1530/ERC-24-0224","DOIUrl":"10.1530/ERC-24-0224","url":null,"abstract":"The association between RET and multiple endocrine neoplasia type 2 was established in 1993 and remains one of the very few oncogenes for which distinct phenotypes (medullary thyroid cancer or pheochromocytoma) are associated with the same hot-spot variants occurring in either germline or somatic DNA. Somatic RET fusion events have also been described in several cancers, including papillary thyroid cancer, non-small-cell lung cancer, breast cancer, salivary gland cancer and pancreatic cancer. Highly selective RET inhibitors have improved outcomes in RET-altered cancers and have been well-tolerated. Nevertheless, primary and acquired drug resistance has been observed, arising from distinct genomic alterations either in RET (on-target resistance) or via alternate oncogenic pathways (bypass resistance). The same mechanisms of resistance have been observed across multiple cancer types, which implies RET-altered cancers evolve away from RET addiction via stochastic subclonal events. Understanding these mechanisms is crucial for identifying therapeutic opportunities to overcome resistance. Successful treatment targeting bypass oncogenes has been reported in several instances, at least for short-term outcomes; in contrast, although several compounds have been reported to overcome on-target RET alterations, none have yet been translated into routine clinical practice and this remains an area of urgent clinical need.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803956","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

Chromosomal alteration patterns in PitNETs: massive losses in aggressive tumors. PitNETs 的染色体畸变模式：侵袭性肿瘤中的大量缺失

Endocrine-related cancer Pub Date : 2024-12-19 Print Date: 2025-01-01 DOI: 10.1530/ERC-24-0070

Maaia Margo Jentus, Leontine Bakker, Marco Verstegen, Iris Pelsma, Tom van Wezel, Dina Ruano, Ellen Kapiteijn, Stijn Crobach, Nienke Biermasz, Hans Morreau

{"title":"Chromosomal alteration patterns in PitNETs: massive losses in aggressive tumors.","authors":"Maaia Margo Jentus, Leontine Bakker, Marco Verstegen, Iris Pelsma, Tom van Wezel, Dina Ruano, Ellen Kapiteijn, Stijn Crobach, Nienke Biermasz, Hans Morreau","doi":"10.1530/ERC-24-0070","DOIUrl":"10.1530/ERC-24-0070","url":null,"abstract":"The molecular biology of pituitary neuroendocrine tumors (PitNETs) revealed few recurrent mutations and extensive chromosomal alterations, with the latter being the driving force in a subset of these lesions. Addressing the need for an easily applicable diagnostic tool, we conducted a retrospective study of 61 PitNETs operated at a tertiary care center. All cases were subtyped according to the 2022 WHO Classification of Endocrine Tumors. A genome-wide next-generation sequencing panel targeting 1500 single nucleotide polymorphisms (SNPs) was used to classify chromosomal imbalances, loss of heterozygosity, and copy number variations in DNA from formalin-fixed paraffin-embedded tissues. We identified four distinct chromosomal patterns, with varying distribution among different tumor lineages. Forty-two of 61 (69%) PitNETs showed chromosomal alterations. Gonadotroph PitNETs showed mostly quiet genomes. The majority of lactotroph PitNETs (19/20, 95%) were altered, exhibiting a gained genome and a remarkably low recurrence rate. Nine of ten (90%) corticotroph PitNETs harbored chromosomal alterations, of which two aggressive corticotroph tumors and one metastatic corticotroph PitNET showed massive chromosomal losses, leading to near-haploid/near-homozygous genomes. The comparison of the molecular profile of primary and recurrent PitNETs of five patients showed no significant accumulation of alterations over time. A simple genome-wide 1500-SNP test can be used in the identification of outspoken aggressive subsets of PitNETs by the occurrence of a near-haploid/near-homozygous genome. Furthermore, the presence of neoplastic tissue in the resected material can be potentially confirmed for non-gonadotroph PitNETs under suboptimal histological assessment conditions.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515229","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

Living with a RET gene mutation: patient perspectives. 与 RET 基因突变共存：患者的观点。

Endocrine-related cancer Pub Date : 2024-12-18 Print Date: 2025-01-01 DOI: 10.1530/ERC-24-0130

Caroline Brain, Joanna Grey, Kirstie Purnell

{"title":"Living with a RET gene mutation: patient perspectives.","authors":"Caroline Brain, Joanna Grey, Kirstie Purnell","doi":"10.1530/ERC-24-0130","DOIUrl":"10.1530/ERC-24-0130","url":null,"abstract":"Multiple endocrine neoplasia type 2 (MEN2) is the collective term for two distinct types of autosomal dominantly inherited neuroendocrine neoplasm syndromes: MEN2A and MEN2B (or MEN3). MEN2 is characterised by medullary thyroid cancer (MTC) (99%) and phaeochromocytoma (50%) and also other conditions according to specific genotype. MEN2A also includes a 25% risk of developing parathyroid hyperplasia and is now recognised as four separate syndromes: classic MEN2A, MEN2A with cutaneous lichen amyloidosis, MEN2A with Hirschsprung's disease and familial MTC. MEN2B accounts for around 5% of all MEN2 cases and predisposes patients to diffuse intestinal ganglioneuromatosis, mucosal neuromas and musculoskeletal abnormalities. MEN2 is autosomal dominantly inherited, meaning that several generations in a single family may be affected by the same syndrome. We present a mini review of four case studies (×2 MEN2A and ×2 MEN2B) that illustrate the advantages of RET testing, as well as some of the likely obstacles that must be overcome to receive a diagnosis of MEN2A or MEN2B. In addition, despite improved genotype/phenotype correlation in MEN2, we highlight that not all cases are 'typical', which emphasises the need for all MEN2 patients to be cared for in a centre of expertise and experience. Some of our case study patients or their parents also took this opportunity to personally tell us more about their lives with MEN2, illustrating the need for more research into the psychosocial impact of these hereditary diseases.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549666","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

Cellular mechanisms of RET receptor dysfunction in multiple endocrine neoplasia 2. 多发性内分泌肿瘤中 RET 受体功能障碍的细胞机制 2.

Endocrine-related cancer Pub Date : 2024-12-13 Print Date: 2025-01-01 DOI: 10.1530/ERC-24-0187

Timothy J Walker, Lois M Mulligan

{"title":"Cellular mechanisms of RET receptor dysfunction in multiple endocrine neoplasia 2.","authors":"Timothy J Walker, Lois M Mulligan","doi":"10.1530/ERC-24-0187","DOIUrl":"10.1530/ERC-24-0187","url":null,"abstract":"Graphical abstract: Abstract: Rearranged during transfection (RET) is a developmentally important receptor tyrosine kinase that has been identified as an oncogenic driver in a number of cancers. Activating RET point mutations gives rise to the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2), characterized by medullary thyroid carcinoma. There are two MEN2 subtypes, MEN2A and MEN2B, that differ in tumour aggressiveness and the associated constellation of other disease features, which are caused by distinct patterns of RET amino acid substitution mutations. MEN2A-RET mutations affecting extracellular cysteine residues promote ligand-independent dimerization and constitutive RET activity, while MEN2B is caused by a single amino acid change in the tyrosine kinase domain of RET, releasing autoinhibition and producing a more active MEN2B-RET kinase that can promote signalling as monomers or dimers in the absence of a ligand. These mutations cause intrinsic biochemical changes in the RET structure and activation but also trigger extrinsic effects that alter RET cellular location, interactions and mechanisms of downregulation that can prolong or mislocate RET activity, changing or enhancing functional outcomes. Furthermore, changes in specific combinations of RET-mediated effects associated with different mutations give rise to the distinct MEN2 disease phenotypes. Here, we discuss the current understanding of the intrinsic and extrinsic characteristics of RET MEN2A cysteine and MEN2B mutants and how these contribute to transforming cellular processes and to the differences in tumour progression and disease aggressiveness.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515228","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

Mechanisms of RET-mediated signal transduction. RET 介导的信号转导机制。

Endocrine-related cancer Pub Date : 2024-12-13 Print Date: 2025-01-01 DOI: 10.1530/ERC-24-0131

Francesca Carlomagno, Marialuisa Moccia, Giorgia Federico, Massimo Santoro

引用次数: 0

ERRATUM: The role of oestrogen receptor α in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2. ERRATUM：雌激素受体α在人类甲状腺癌中的作用：核心调节蛋白和酪氨酸激酶受体HER2的贡献。

Endocrine-related cancer Pub Date : 2024-11-25 DOI: 10.1530/ERC-09-0216e

Dara O Kavanagh, Marie McIlroy, Eddie Myers, Fiona Bane, Thomas B Crotty, E McDermott, Arnold D Hill, Leonie S Young

引用次数: 0

AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma. AGO2 蛋白：作为肾上腺皮质癌新型生物标志物的 miRNA 通路中的一个关键酶。

Endocrine-related cancer Pub Date : 2024-11-20 Print Date: 2024-12-01 DOI: 10.1530/ERC-24-0061

Anila Hashmi, Alexander Papachristos, Stan Sidhu, Gyorgy Hutvagner

{"title":"AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma.","authors":"Anila Hashmi, Alexander Papachristos, Stan Sidhu, Gyorgy Hutvagner","doi":"10.1530/ERC-24-0061","DOIUrl":"10.1530/ERC-24-0061","url":null,"abstract":"Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy characterized by diagnostic challenges, high recurrence rates, and poor prognosis. This study explored the role of miRNA processing genes in ACC and their potential role as diagnostic and prognostic biomarkers. We analyzed the mRNA expression levels of miRNA machinery components (DROSHA, DGCR8, XPO5, RAN, DICER, TARBP2, and AGO2) utilizing mRNA-Seq data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) projects. Additionally, protein levels were quantified in tissue samples from the Kolling Institute of Medical Research's tumor bank. Our results demonstrated that among all miRNA processing components, AGO2 exhibited significant overexpression in ACC compared to the normal adrenal cortex and benign adrenal adenoma (P < 0.001). Kaplan-Meier survival analysis indicated that higher AGO2 expression correlated with significantly worse overall survival in ACC patients (HR: 7.07, P < 0.001). Among 32 cancer types in TCGA, the prognostic significance of AGO2 was most prominent in ACC. This study is the first to report AGO2's potential as a diagnostic and prognostic biomarker in ACC, emphasizing its significance in ACC pathogenesis and potential application as a non-invasive liquid biopsy biomarker.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484030","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

Impact of age on genomic alterations and the tumor immune microenvironment in papillary thyroid cancer. 年龄对甲状腺乳头状癌基因组改变和肿瘤免疫微环境的影响

Endocrine-related cancer Pub Date : 2024-11-04 Print Date: 2024-12-01 DOI: 10.1530/ERC-23-0341

Dominique D Liddy, Zhongyue Zhang, Kalyanee Shirlekar, Zhongping He, Kelly M Herremans, Song Han, Jason O Brant, Francis D Moore, Steven J Hughes, Aditya S Shirali

{"title":"Impact of age on genomic alterations and the tumor immune microenvironment in papillary thyroid cancer.","authors":"Dominique D Liddy, Zhongyue Zhang, Kalyanee Shirlekar, Zhongping He, Kelly M Herremans, Song Han, Jason O Brant, Francis D Moore, Steven J Hughes, Aditya S Shirali","doi":"10.1530/ERC-23-0341","DOIUrl":"10.1530/ERC-23-0341","url":null,"abstract":"Differentiated thyroid cancer in older adults has been linked to alterations in the mutational landscape and tumor immune cell infiltration that create a tumor-permissive microenvironment. We sought to determine the impact of age on genomic alterations and immune cell composition in papillary thyroid cancer (PTC). Genomic alterations, immune cell composition, and clinical data were obtained using The Cancer Genome Atlas and computational immunogenomic analyses. Disease severity was recoded into three groups: Group A (T1-2N0M0), Group B (T1-3N1a-1bM0), and Group C (T4NxMx or TxNxM1). Histopathologic subtypes included conventional, follicular-variant, and tall cell variant PTC. Spearman's rank correlation, ANOVA, t-test, and multivariable linear regression were performed. A total of 470 PTC samples were retrieved from the TCGA portal with genomic alteration and immune cell composition data. TERT promoter alterations were more common in patients aged ≥65 years (26% vs 4%, P < 0.0001). Tumor mutational burden increased with increasing age (r = 0.463, P < 0.0001). Increasing age was associated with decreased CD8+ T cells (r = -0.15, P = 0.01) using CIBERSORT and decreased B cells (r = -0.13), CD8+ T cells (r = -0.19), and neutrophils (r = -0.14, P < 0.05) using TIMER. Multivariate regression found that increasing age was independently associated with increased resting NK cells and resting dendritic cells, and decreased naïve B cells and CD8+ T cells (P < 0.05). PTC tumors of older adults are characterized by increased TERT promoter alterations, increased tumor mutational burden, and a decreased cytotoxic CD8+ T cells and increased resting dendritic cell immune infiltrate. Further studies are needed to determine if these changes in immune cell infiltrate are associated with compromised outcomes.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309472","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

Evaluating the prognostic potential of circulating cell-free DNA in advanced thyroid cancer. 评估晚期甲状腺癌循环游离 DNA 的预后潜力

Endocrine-related cancer Pub Date : 2024-11-01 DOI: 10.1530/ERC-24-0227

Ayanthi Wijewardene, Roderick J Clifton-Bligh, Bin Wang, Catherine Luxford, Bruce G Robinson, Martyn Bullock, Matti Gild

{"title":"Evaluating the prognostic potential of circulating cell-free DNA in advanced thyroid cancer.","authors":"Ayanthi Wijewardene, Roderick J Clifton-Bligh, Bin Wang, Catherine Luxford, Bruce G Robinson, Martyn Bullock, Matti Gild","doi":"10.1530/ERC-24-0227","DOIUrl":"https://doi.org/10.1530/ERC-24-0227","url":null,"abstract":"Liquid biopsies are a minimally invasive approach to obtain biomarkers including cell free DNA (cfDNA) from peripheral blood. Our study evaluated the utility of cfDNA in advanced thyroid cancers. Patients aged >18 years with metastatic medullary thyroid cancer (MTC), poorly differentiated thyroid cancer (PDTC), or anaplastic thyroid cancer (ATC) were enrolled in this prospective study between 2020 and 2024. As part of standard care, sequencing of germline and tumoral DNA was conducted, and patients with germline mutations were excluded from the study. Whole blood samples were collected in Streck cell-free DNA BCT tubes, cfDNA was extracted from plasma using the EZ1and2 ccfDNA kit and EZ2 Connect. The extracted cfDNA was then sequenced across 50 key cancer-related genes using the Oncomine Precision Assay (OPA) panel on an Ion Torrent Genexus Integrated Sequencer. Forty patients were included; 27 MTC, 2 ATC and 11 PDTC. Tumoral mutations were detected in 36 of the included patients (90%): cfDNA detected mutations in 18/36 patients (13 MTC, 1 ATC, 4 PDTC (50%). Sensitivity of cfDNA was 86% (6/7) pre TKI therapy, and reduced to 54% on therapy (13/24), suggestive of lack of tumor-derived DNA shedding with strong on-target treatment efficacy. Median cfDNA concentration was higher in samples with a detected mutation than those without, 11.91 ng/ml vs 5.81 ng/ml respectively. While an increasing cfDNA was associated with worse progression free survival (p < 0.01). cfDNA is a novel biomarker with potential to monitor disease progression in patients with advanced thyroid cancers.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741786","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