Endocrine oncology (Bristol, England)最新文献

{"title":"Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.","authors":"Emma Boehm, Terry Hung, Tim Akhurst, Ramin Alipour, Cherie Chiang, Rodney J Hicks, Michael S Hofman, Aravind S Ravi Kumar, Nirupa Sachithanandan, Javad Saghebi, Michael Michael, Grace Kong","doi":"10.1530/EO-24-0013","DOIUrl":"10.1530/EO-24-0013","url":null,"abstract":"<p><strong>Background: </strong>Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes. Peptide receptor radionuclide therapy (PRRT) is a rational option for hormone and disease control in ECS caused by NEN with high somatostatin receptor (SSTR) expression.</p><p><strong>Aim: </strong>To describe the characteristics and outcomes of patients with ECS treated with PRRT.</p><p><strong>Methods: </strong>Single-centre, retrospective analysis of imaging, biochemistry and outcomes of seven consecutive patients with ECS caused by metastatic GEPNEN treated with PRRT from 2006 to 2023.</p><p><strong>Results: </strong>Patients were aged 17-75 (female <i>n</i> = 6). The primary site was the pancreas (5/7) and rectum (2/7). Six patients were on medical therapy for ECS at baseline (one had a previous BA). A median of 34.4 GBq of [¹⁷⁷Lu]Lu-DOTA-octreotate was given. [⁹⁰Y]Y-DOTA-octreotate (one patient) and [¹¹¹In]In-octreotide (one patient) were also used. Five patients had radiosensitising chemotherapy. Five patients had a flare of ECS within 1 week of PRRT cycle 1 (PRRT-C1). Following PRRT-C1, 5/7 patients had complete biochemical resolution of ECS at 1.5-6 months (four ongoing; one recurred after 12 months and had elective BA at 18 months). Best metabolic response on [¹⁸F]F-FDG PET/CT: Four patients had a complete metabolic response (CMR), and one had a partial metabolic response. PFS was 3-208 months. Two patients progressed at the first follow-up. The longest ECS remission and CMR continues at >17 years.</p><p><strong>Conclusion: </strong>PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240013"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795692","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":"Less frequent radiological exams to avoid futile response assessments from 177-LuDOTATE therapy for patients with advanced neuroendocrine tumors.","authors":"Carolina C Marques, Angelo B Brito, Eduardo N Lima, Mauro D Donadio, Rachel P Riechelmann","doi":"10.1530/EO-24-0021","DOIUrl":"10.1530/EO-24-0021","url":null,"abstract":"<p><strong>Background: </strong>177-LuDOTATE is an effective but expensive treatment for neuroendocrine tumors (NETs). Reducing treatment-related costs, such as the number of images, could improve access to 177-LuDOTATE. We evaluated early radiological tumor progression and prognostic factors in patients with NETs treated with 177-LuDOTATE.</p><p><strong>Methods: </strong>We retrospectively included all patients with NETs who received at least one cycle of 177-LuDOTATE. The primary endpoint was the rate of early radiological progression between cycles 2 and 3 (in 10-16 weeks). Secondary endpoints were progression-free survival (PFS) and overall survival (OS) according to prognostic factors (tumor grade, primary site, functioning syndrome, 177-LuDOTATE treatment line) in Cox proportional hazards models.</p><p><strong>Results: </strong>The median number of 177-LuDOTATE cycles was 3 (range 1-6) among 59 patients included. Ten (17%) patients had early progression. Among 14 patients who received ≤2 cycles of 177-LuDOTATE, ten (72%) stopped treatment due to disease progression, with five patients having a G2 (ki67: 5-25%) and 4, a G3 (ki67: 25-90%) NET. In the Cox multivariable analysis, higher grade (G2 or G3 vs G1) were significantly associated with inferior PFS and OS. The median PFS of G1, G2 and G3 NET patients were: 34.1, 11.7 and 6.1 months (<i>P</i> = 0.015), respectively.</p><p><strong>Conclusions: </strong>It is feasible to perform imaging tests after 177-LuDOTATE completion for patients with indolent NETs with the intent to avoid futile assessments. For patients with more aggressive diseases, such as G3 NETs and G2 tumors with high tumor burden, we advise to perform more frequent images during 177-LuDOTATE therapy.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240021"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634022","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":"Hereditary and clinical insights into paraganglioma and pheochromocytoma.","authors":"Caitlin B Mauer Hall, Elise M Watson, Tanushree Prasad, Chandler L Myers, Jacqueline A Mersch","doi":"10.1530/EO-24-0029","DOIUrl":"10.1530/EO-24-0029","url":null,"abstract":"<p><strong>Background: </strong>Approximately 30-40% of paragangliomas (PGLs) and pheochromocytomas (PCCs) harbor an underlying hereditary cause. Early identification of at-risk individuals is imperative given the early onset, aggressiveness of tumors, and other tumor/cancer risks associated with hereditary PGLs/PCCs. This study analyzes the clinical presentations and genetic histories of patients with PGL/PCC and/or hereditary risk to contribute to the expanding knowledge in this rare population.</p><p><strong>Methods: </strong>A retrospective chart review identified two cohorts of patients seen in cancer genetics clinics at an academic medical center and a safety-net hospital between August 2016 and December 2022. Cohort 1 consisted of patients with likely pathogenic variants (LPVs)/pathogenic variants (PVs) in hereditary PGL/PCC predisposition genes. Cohort 2 consisted of patients with a personal history of a PGL/PCC. Demographics, personal/family history, and genetic testing outcomes were analyzed.</p><p><strong>Results: </strong>A total of 560 patients met the study criteria (Cohort 1, <i>n</i> = 364; Cohort 2, <i>n</i> = 269). In Cohort 1, 77 (21.1%) patients had an incidental LPV/PV in a PGL/PCC gene. Nearly half (<i>n</i> = 36, 46.8%) were in <i>SDHx</i> genes, with a majority in <i>SDHA</i> (<i>n</i> = 21). In Cohort 2, 86 patients tested positive for 87 LPV/PV in a hereditary cancer predisposition gene. The <i>SDHx</i> genes were most likely to have an LPV/PV identified (<i>SDHB n</i> = 24, <i>SDHD n</i> = 23).</p><p><strong>Conclusions: </strong>Multigene panels identify patients at risk for hereditary PGL/PCC, many of whom are incidentally found. While <i>SDHA</i> LPV/PVs were the most frequent incidental finding, they were less common in patients with PGL/PCC, indicating the need for longitudinal studies to better understand the prevalence and penetrance of these tumors.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240029"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633926","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":"Pituitary gigantism due to a novel <i>AIP</i> germline splice-site variant.","authors":"Elisa Lamback, Renan Lyra Miranda, Leila Chimelli, Felipe Andreiuolo, Leandro Kasuki, Luiz Eduardo Wildemberg, Mônica R Gadelha","doi":"10.1530/EO-24-0003","DOIUrl":"10.1530/EO-24-0003","url":null,"abstract":"<p><p>Pituitary gigantism is a rare pediatric disorder caused by excess growth hormone (GH) secretion. In almost 50% of cases, a genetic cause can be identified, with pathogenic variants in the aryl hydrocarbon receptor-interacting protein (<i>AIP</i>) gene being the most common. We present a case of an 11-year-old boy who exhibited progressive vision loss, associated with accelerated linear growth, and weight gain. On physical examination, he had enlarged hands, right eye amaurosis, and was already above his target height. Increased GH and IGF-I concentrations confirmed the diagnosis of pituitary gigantism. Magnetic resonance imaging showed a giant sellar lesion with supra- and para-sellar extensions. He underwent two surgeries which did not achieve a cure or visual improvement. Histopathological analysis revealed a sparsely granulated tumor, negative for somatostatin receptor type 2 (SST2) and an immunoreactivity score of 6 for somatostatin receptor type 5 (SST5). Our published artificial intelligence prediction model predicted an 83% chance of not responding to first-generation somatostatin receptor ligands. Pasireotide was therefore prescribed, and afterward cabergoline was added on. IGF-I concentrations decreased but did not normalize. We discovered a novel germline single nucleotide variant in the splicing donor region of intron 2 of the <i>AIP</i> gene (NM_003977.4:c.279+1 G>A), classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240003"},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402211","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":"Differential utilization of thyroid lobectomy after the 2015 American Thyroid Association guideline update.","authors":"Patricia Gina Lu, Zhi Ven Fong, Patrick T Hangge, Yu-Hui Chang, Elisabeth S Lim, Nabil Wasif, Patricia A Cronin, Chee-Chee Stucky","doi":"10.1530/EO-24-0010","DOIUrl":"10.1530/EO-24-0010","url":null,"abstract":"<p><strong>Background: </strong>The 2015 American Thyroid Association (ATA) guidelines added thyroid lobectomy (TL) as the appropriate treatment for low-risk differentiated thyroid cancer (DTC). We aimed to investigate the population-level factors that influence the utilization of TL.</p><p><strong>Methods: </strong>The Surveillance, Epidemiology and End Results (SEER) database was queried for all DTC patients fitting low-risk criteria as defined by the ATA. Trends in total thyroidectomy (TT) and TL were identified using a Cochrane-Armitage test. Multivariable logistic regression identified patient and socioeconomic characteristics associated with TL, and difference-in-difference analysis was used to control for secular trends over time.</p><p><strong>Results: </strong>A total of 43,526 patients with low-risk DTC were identified in the SEER database; 39,411 pre-2015 and 4115 post-2015. After 2015, TT continued to outnumber TL (76.2% vs 23.8%), although the rate of TL increased significantly (11.6% to 23.8%, <i>P</i> < 0.001). However, difference-in-difference analysis found that age > 55 (OR 1.11, 95% CI 1.01-1.19, <i>P</i> < 0.001) and rurality (OR 1.16, 95% CI 1.05-1.28, <i>P</i> < 0.001) were independently associated with TT. TL was associated with T1 disease (OR 1.11, 95% CI 1.04-1.19, <i>P</i> = 0.001).</p><p><strong>Conclusion: </strong>Although the 2015 ATA guideline update led to an increase in TL for low-risk DTC, most patients still underwent TT. Age and neighborhood significantly impact the odds of receiving guideline-appropriate TL for low-risk DTC, especially for T2 disease.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240010"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156837","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":"Histopathological analysis potential for unveiling hormone signaling in endocrine-related tumors.","authors":"Yasuhiro Miki, Erina Iwabuchi, Chihiro Inoue, Yuto Yamazaki, Takashi Suzuki","doi":"10.1530/EO-24-0033","DOIUrl":"10.1530/EO-24-0033","url":null,"abstract":"<p><p>Elucidating the mechanisms of action of steroid hormones will contribute to the development of therapeutic strategies for hormone-dependent tumors. Recent advances in genetic engineering have revealed the complex and diverse mechanisms of steroid hormone signaling; however, these techniques are limited to <i>in vitro</i> or animal experiments. It is believed that verifying hormone signals elucidated using human pathological tissue specimens will directly aid in treatment and diagnosis. However, pathological tissue specimens are generally formalin-fixed paraffin-embedded (FFPE), and protein/gene analyses of FFPE tissues are limited. Protein detection using immunohistochemistry with specific antibodies in FFPE tissues is a classical technique essential for diagnosis and treatment decisions in various types of cancer. In steroid hormone signaling, the expression and localization of receptors, hormone-related enzymes, and proteins encoded by response genes can be clarified using immunohistochemistry. Although protein-protein interactions such as receptor dimers and DNA-binding proteins are mainly detected <i>in vitro</i>, they can be examined in FFPE tissues using <i>in situ</i> proximity ligation assays and southwestern histochemistry, respectively. Using these detection methods, including immunohistochemistry, it is possible to analyze each hormone signaling pathway in hormone-related tumors histopathologically. Although FFPE tissues still suffer from gene and protein denaturation, their advantages include the ability to retrospectively study target factors/signals and obtain spatial information through microscopy. This review describes a visualization method for elucidating steroid hormone signaling in hormone-dependent tumors using FFPE tissues.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240033"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156838","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":"Adrenocortical carcinoma: selective internal radiation therapy and liver metastases.","authors":"Leo Baxendale-Smith, Karim El-Shakankery, James Gordon-Smith, Lucy Wall","doi":"10.1530/EO-23-0041","DOIUrl":"10.1530/EO-23-0041","url":null,"abstract":"<p><p>Selective internal radiation therapy (SIRT) is a novel intervention for both primary and metastatic malignant liver lesions. Adrenocortical carcinoma (ACC) is rare with limited treatment options; evidence for SIRT in ACC liver metastases consists of case reports only. Selective internal radiation therapy (SIRT) was employed to treat recurrent liver metastases in a 49-year-old gentleman with ACC, who previously underwent a left-sided hepatectomy. The patient opted for SIRT after reviewing the literature regarding mitotane chemotherapy and its toxicities. Selective internal radiation therapy (SIRT) provided several months of progression-free survival (PFS), with no toxicity and an excellent radiological response. The patient re-presented 12 years after the initial diagnosis with skeletal metastases and sadly died in September 2022. Substantial unmet need exists for effective treatments in ACC, with 75% of patients presenting with incurable disease. Developing widespread disease, SIRT offered 2 years' PFS in our patient; this was well tolerated with minimal residual liver impairment. Its use in ACC liver-limited disease warrants investigation.</p><p><strong>Significance statement: </strong>Adrenocortical carcinoma (ACC) is a rare and aggressive tumour with limited treatments. Once metastatic disease develops, existing standard-of-care treatments offer a dismal overall survival, alongside marked toxicities. Selective internal radiation therapy (SIRT) may represent a new intervention in the treatment paradigm for liver-limited, metastatic ACC. Here, we present the case of a patient treated with multiple rounds of SIRT for relapsed, liver-limited ACC, prolonging survival by several years. Recurrent SIRT led to maintained liver function and no toxicities. Little evidence outlines its use in ACC but further study is certainly warranted to ascertain the value of SIRT, considering the limited treatment landscape that currently exists.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e230041"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899100","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":"Tolerability and outcomes of neuroendocrine tumors treated with PRRT and SBRT.","authors":"Jose E Nunez, Sylvia Ng, Hanbo Chen, Simron Singh, Julie Hallet, Calvin Law, Sten Myrehaug","doi":"10.1530/EO-24-0001","DOIUrl":"10.1530/EO-24-0001","url":null,"abstract":"<p><p>There is interest in optimizing peptide receptor radionuclide therapy (PRRT) for the management of metastatic neuroendocrine neoplasms (NEN). The addition of stereotactic body radiation therapy (SBRT) may provide synergistic benefits by targeting specific sites of disease that may represent areas of tumor heterogeneity. Little is known about the efficacy or potential toxicity of this approach; understanding the outcomes of patients treated with these two modalities in a sequential fashion will provide insights into the appropriateness of embarking on a combined therapy strategy. An institutional retrospective review of 21 patients with NEN treated with sequential PRRT and SBRT (64 targets) was performed. Median overall survival and progression-free survival were 19.6 months and 12.8 months, respectively. Median time to local recurrence at the SBRT site was not reached, with rates at 12 and 24 months of 1.8% and 5.9%, respectively. The toxicity profile remains favorable. Given the safety and efficacy of sequential SBRT and PRRT, further trials evaluating a concurrent treatment approach may be warranted.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240001"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899345","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":"Metyrosine-associated endocrinological changes in pheochromocytoma and paraganglioma.","authors":"Yuko Matsuo,&nbsp;Kenji Ashida,&nbsp;Ayako Nagayama,&nbsp;Kanoko Moritaka,&nbsp;Mizuki Gobaru,&nbsp;Junichi Yasuda,&nbsp;Naoyuki Ogasawara,&nbsp;Hirofumi Kurose,&nbsp;Katsuaki Chikui,&nbsp;Shimpei Iwata,&nbsp;Yukihiro Inoguchi,&nbsp;Nao Hasuzawa,&nbsp;Seiichi Motomura,&nbsp;Tsukasa Igawa,&nbsp;Masatoshi Nomura","doi":"10.1530/EO-23-0006","DOIUrl":"https://doi.org/10.1530/EO-23-0006","url":null,"abstract":"<p><strong>Objective: </strong>Metyrosine (alpha-methyl-para-tyrosine) effectively reduces catecholamine levels in patients with pheochromocytoma/paraganglioma. However, improvements in physiological and metabolic parameters and changes in endocrine function associated with metyrosine administration should be validated in comparison to surgery. This study was performed to confirm the effects of metyrosine on the physiological, metabolic, and endocrinological functions of patients with pheochromocytoma/paraganglioma in the perioperative period.</p><p><strong>Design: </strong>This retrospective cohort study was performed at a single university hospital.</p><p><strong>Methods: </strong>We included ten patients with pheochromocytoma/paraganglioma who received oral metyrosine after α-blocker therapy and consecutive surgeries. Urinary catecholamine metabolite levels and other clinical parameters were evaluated before and after metyrosine administration, and 1 week after surgery.</p><p><strong>Results: </strong>The mean age was 53.1 ± 16.1 years. Of the ten participants (four men and six women), nine had pheochromocytoma and one had paraganglioma. The median maximum metyrosine dose was 750 mg/day. Urinary catecholamine metabolite levels significantly decreased in a dose-dependent manner after metyrosine administration. Both systolic and diastolic blood pressure significantly decreased after metyrosine and surgical treatment. Metyrosine administration significantly improved insulin sensitivity, although surgery improved the the basal insulin secretion. Additionally, serum prolactin and thyroid-stimulatory hormone levels were significantly increased by metyrosine treatment, whereas plasma renin activity was decreased.</p><p><strong>Conclusions: </strong>Metyrosine significantly reduced catecholamines in patients with pheochromocytoma/paraganglioma and ensured the safety of the surgery. Adjustment of metyrosine administration may make surgical pretreatment more effective in achieving stabilized blood pressure and improving glucose metabolism. Endocrine parameters may manifest as the systemic effects of metyrosine administration.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"3 1","pages":"e230006"},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222010","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":"Peptides disrupting TM4SF3 interaction with AR or AR-V7 block prostate cancer cell proliferation.","authors":"Prabesh Khatiwada,&nbsp;Ujjwal Rimal,&nbsp;Mamata Malla,&nbsp;Zhengyang Han,&nbsp;Lirim Shemshedini","doi":"10.1530/EO-23-0010","DOIUrl":"10.1530/EO-23-0010","url":null,"abstract":"<p><p>Androgen receptor (AR) plays a vital role in the development and progression of prostate cancer from the primary stage to the usually lethal stage known as castration-resistant prostate cancer (CRPC). Constitutively active AR splice variants (AR-Vs) lacking the ligand-binding domain are partially responsible for the abnormal activation of AR and may be involved in resistance to AR-targeting drugs occurring in CRPC. There is increasing consensus on the potential of drugs targeting protein-protein interactions. Our lab has recently identified transmembrane 4 superfamily 3 (TM4SF3) as a critical interacting partner for AR and AR-V7 and mapped the minimal interaction regions. Thus, we hypothesized that these interaction domains can be used to design peptides that can disrupt the AR/TM4SF3 interaction and kill prostate cancer cells. Peptides TA1 and AT1 were designed based on the TM3SF3 or AR interaction domain, respectively. TA1 or AT1 was able to decrease AR/TM4SF3 protein interaction and protein stability. Peptide TA1 reduced the recruitment of AR and TM4SF3 to promoters of androgen-regulated genes and subsequent activation of these AR target genes. Peptides TA1 and AT1 were strongly cytotoxic to prostate cancer cells that express AR and/or AR-V7. Peptide TA1 inhibited the growth and induced apoptosis of both enzalutamide-sensitive and importantly enzalutamide-resistant prostate cancer cells. TA1 also blocked the migration and malignant transformation of prostate cancer cells. Our data clearly demonstrate that using peptides to target the important interaction AR has with TM4SF3 provides a novel method to kill enzalutamide-resistant prostate cancer cells that can potentially lead to new more effective therapy for CRPC.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"3 1","pages":"e230010"},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/29/EO-23-0010.PMC10563598.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222011","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}