Levent Mutlu, Blair McNamara, Stefania Bellone, Diego D Manavella, Cem Demirkiran, Michelle Greenman, Miguel Skyler Z Verzosa, Natalia Buza, Pei Hui, Tobias Max Philipp Hartwich, Justin Harold, Yang Yang-Hartwich, Margherita Zipponi, Gary Altwerger, Elena Ratner, Gloria S Huang, Mitchell Clark, Vaagn Andikyan, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
{"title":"Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2.","authors":"Levent Mutlu, Blair McNamara, Stefania Bellone, Diego D Manavella, Cem Demirkiran, Michelle Greenman, Miguel Skyler Z Verzosa, Natalia Buza, Pei Hui, Tobias Max Philipp Hartwich, Justin Harold, Yang Yang-Hartwich, Margherita Zipponi, Gary Altwerger, Elena Ratner, Gloria S Huang, Mitchell Clark, Vaagn Andikyan, Masoud Azodi, Peter E Schwartz, Alessandro D Santin","doi":"10.1007/s10585-024-10297-z","DOIUrl":"10.1007/s10585-024-10297-z","url":null,"abstract":"<p><p>High-grade serous ovarian cancer (HGSOC) and ovarian clear cell carcinoma (CC), are biologically aggressive tumors endowed with the ability to rapidly metastasize to the abdominal cavity and distant organs. About 10% of HGSOC and 30% of CC demonstrate HER2 IHC 3 + receptor over-expression. We evaluated the efficacy of trastuzumab deruxtecan (T-DXd; DS-8201a), a novel HER2-targeting antibody-drug conjugate (ADC) to an ADC isotype control (CTL ADC) against multiple HGSOC and CC tumor models. Eleven ovarian cancer cell lines including a matched primary and metastatic cell line established from the same patient, were evaluated for HER2 expression by immunohistochemistry and flow cytometry, and gene amplification by fluorescence in situ hybridization assays. In vitro experiments demonstrated T-DXd to be significantly more effective against HER2 3 + HGSOC and CC cell lines when compared to CTL ADC (p < 0.0001). T-DXd induced efficient bystander killing of HER2 non-expressing tumor cells when admixed with HER2 3 + cells. In vivo activity of T-DXd was studied in HER2 IHC 3 + HGSOC and CC mouse xenograft models. We found T-DXd to be significantly more effective than CTL ADC against HER2 3 + HGSOC (KR(CH)31) and CC (OVA10) xenografts with a significant difference in tumor growth starting at day 8 (p = 0.0003 for KR(CH)31, p < 0.0001 for OVA10). T-DXd also conferred a survival advantage in both xenograft models. T-DXd may represent an effective ADC against primary and metastatic HER2-overexpressing HGSOC and CC.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"765-775"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D Pezzulla, G Chiloiro, E M Lima, G Macchia, C Romano, S Reina, G Panza, S Cilla, A G Morganti, F Cellini, M A Gambacorta, F Deodato
{"title":"Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.","authors":"D Pezzulla, G Chiloiro, E M Lima, G Macchia, C Romano, S Reina, G Panza, S Cilla, A G Morganti, F Cellini, M A Gambacorta, F Deodato","doi":"10.1007/s10585-024-10301-6","DOIUrl":"10.1007/s10585-024-10301-6","url":null,"abstract":"<p><p>A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67 years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50 Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32 Gy). The treatment response at 3-4 months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"667-678"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophia Leduc, Ha-Linh Nguyen, François Richard, Gitte Zels, Amena Mahdami, Maxim De Schepper, Marion Maetens, Anirudh Pabba, Joris Jaekers, Emily Latacz, Ali Bohlok, Evy Vanderheyden, Thomas Van Brussel, Bram Boeckx, Rogier Schepers, Diether Lambrechts, Luc Dirix, Denis Larsimont, Sophie Vankerckhove, Valerio Lucidi, Baki Topal, Imane Bachir, Vincent Donckier, Giuseppe Floris, Peter Vermeulen, Christine Desmedt
{"title":"Transcriptomic characterization of the histopathological growth patterns in breast cancer liver metastases.","authors":"Sophia Leduc, Ha-Linh Nguyen, François Richard, Gitte Zels, Amena Mahdami, Maxim De Schepper, Marion Maetens, Anirudh Pabba, Joris Jaekers, Emily Latacz, Ali Bohlok, Evy Vanderheyden, Thomas Van Brussel, Bram Boeckx, Rogier Schepers, Diether Lambrechts, Luc Dirix, Denis Larsimont, Sophie Vankerckhove, Valerio Lucidi, Baki Topal, Imane Bachir, Vincent Donckier, Giuseppe Floris, Peter Vermeulen, Christine Desmedt","doi":"10.1007/s10585-024-10279-1","DOIUrl":"10.1007/s10585-024-10279-1","url":null,"abstract":"<p><p>Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"699-705"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessandro Rizzo, Sebastiano Buti, Patrizia Giannatempo, Samer Salah, Javier Molina-Cerrillo, Francesco Massari, Ray Manneh Kopp, Ondřej Fiala, Luca Galli, Zin W Myint, Deniz Tural, Andrey Soares, Renate Pichler, Alessia Mennitto, Halima Abahssain, Fabio Calabrò, Fernando Sabino M Monteiro, Anna Albano, Veronica Mollica, Giulia Claire Giudice, Hideki Takeshita, Matteo Santoni
{"title":"Pembrolizumab in patients with advanced upper tract urothelial carcinoma: a real-world study from ARON-2 project.","authors":"Alessandro Rizzo, Sebastiano Buti, Patrizia Giannatempo, Samer Salah, Javier Molina-Cerrillo, Francesco Massari, Ray Manneh Kopp, Ondřej Fiala, Luca Galli, Zin W Myint, Deniz Tural, Andrey Soares, Renate Pichler, Alessia Mennitto, Halima Abahssain, Fabio Calabrò, Fernando Sabino M Monteiro, Anna Albano, Veronica Mollica, Giulia Claire Giudice, Hideki Takeshita, Matteo Santoni","doi":"10.1007/s10585-024-10296-0","DOIUrl":"10.1007/s10585-024-10296-0","url":null,"abstract":"<p><p>Upper tract urothelial carcinoma (UTUC) accounts for the 5-10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6-12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9-6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"655-665"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"GFPT2 expression is induced by gemcitabine administration and enhances invasion by activating the hexosamine biosynthetic pathway in pancreatic cancer.","authors":"Kent Miyazaki, Kyohei Ariake, Satoko Sato, Takayuki Miura, Jingyu Xun, Daisuke Douchi, Masaharu Ishida, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Takashi Kamei, Michiaki Unno","doi":"10.1007/s10585-024-10298-y","DOIUrl":"10.1007/s10585-024-10298-y","url":null,"abstract":"<p><p>Our previous studies revealed a novel link between gemcitabine (GEM) chemotherapy and elevated glutamine-fructose-6-phosphate transaminase 2 (GFPT2) expression in pancreatic cancer (PaCa) cells. GFPT2 is a rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP). HBP can enhance metastatic potential by regulating epithelial-mesenchymal transition (EMT). The aim of this study was to further evaluate the effect of chemotherapy-induced GFPT2 expression on metastatic potential. GFPT2 expression was evaluated in a mouse xenograft model following GEM exposure and in clinical specimens of patients after chemotherapy using immunohistochemical analysis. The roles of GFPT2 in HBP activation, downstream pathways, and cellular functions in PaCa cells with regulated GFPT2 expression were investigated. GEM exposure increased GFPT2 expression in tumors resected from a mouse xenograft model and in patients treated with neoadjuvant chemotherapy (NAC). GFPT2 expression was correlated with post-operative liver metastasis after NAC. Its expression activated the HBP, promoting migration and invasion. Treatment with HBP inhibitors reversed these effects. Additionally, GFPT2 upregulated ZEB1 and vimentin expression and downregulated E-cadherin expression. GEM induction upregulated GFPT2 expression. Elevated GFPT2 levels promoted invasion by activating the HBP, suggesting the potential role of this mechanism in promoting chemotherapy-induced metastasis.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"777-789"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"UBTF mediates activation of L3MBTL2 to suppress NISCH expression through histone H2AK119 monoubiquitination modification in breast cancer.","authors":"Kun Chen, Yun Dong, Gaojian He, Xuefeng He, Meitong Pan, Xuemei Huang, Xiaolan Yu, Jiyi Xia","doi":"10.1007/s10585-024-10299-x","DOIUrl":"10.1007/s10585-024-10299-x","url":null,"abstract":"<p><p>Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2) has been related to transcriptional inhibition and chromatin compaction. Nevertheless, the biological functions and mechanisms of L3MBTL2 are undefined in breast cancer (BRCA). Here, we revealed that L3MBTL2 is responsible for the decline of Nischarin (NISCH), a well-known tumor suppressor, in BRCA, and explored the detailed mechanism. Knockdown of L3MBTL2 reduced monoubiquitination of histone H2A at lysine-119 (H2AK119ub), leading to reduced binding to the NISCH promoter and increased expression of NISCH. Meanwhile, the knockdown of L3MBTL2 decreased proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of BRCA cells, and increased apoptosis, which were abated by NISCH knockdown. Nucleolar transcription factor 1 (UBTF) induced the transcription of L3MBTL2 in BRCA, and the suppressing effects of UBTF silencing on EMT in BRCA cells were also reversed by NISCH knockdown. Knockdown of UBTF slowed tumor progression and attenuated lung tumor infiltration, whereas simultaneous knockdown of NISCH accelerated EMT and increased tumor lung metastasis. Taken together, our results show that L3MBTL2, transcriptionally activated by UBTF, exerts oncogenic functions in BRCA, by catalyzing H2AK119Ub and reducing expression of NISCH.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"791-805"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Libring, Emily D Berestesky, Cynthia A Reinhart-King
{"title":"The movement of mitochondria in breast cancer: internal motility and intercellular transfer of mitochondria.","authors":"Sarah Libring, Emily D Berestesky, Cynthia A Reinhart-King","doi":"10.1007/s10585-024-10269-3","DOIUrl":"10.1007/s10585-024-10269-3","url":null,"abstract":"<p><p>As a major energy source for cells, mitochondria are involved in cell growth and proliferation, as well as migration, cell fate decisions, and many other aspects of cellular function. Once thought to be irreparably defective, mitochondrial function in cancer cells has found renewed interest, from suggested potential clinical biomarkers to mitochondria-targeting therapies. Here, we will focus on the effect of mitochondria movement on breast cancer progression. Mitochondria move both within the cell, such as to localize to areas of high energetic need, and between cells, where cells within the stroma have been shown to donate their mitochondria to breast cancer cells via multiple methods including tunneling nanotubes. The donation of mitochondria has been seen to increase the aggressiveness and chemoresistance of breast cancer cells, which has increased recent efforts to uncover the mechanisms of mitochondrial transfer. As metabolism and energetics are gaining attention as clinical targets, a better understanding of mitochondrial function and implications in cancer are required for developing effective, targeted therapeutics for cancer patients.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"567-587"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filippo Merloni, Michela Palleschi, Caterina Gianni, Marianna Sirico, Riccardo Serra, Chiara Casadei, Samanta Sarti, Lorenzo Cecconetto, Giandomenico Di Menna, Marita Mariotti, Roberta Maltoni, Daniela Montanari, Antonino Romeo, Ugo De Giorgi
{"title":"Local treatment for oligoprogressive metastatic sites of breast cancer: efficacy, toxicities and future perspectives.","authors":"Filippo Merloni, Michela Palleschi, Caterina Gianni, Marianna Sirico, Riccardo Serra, Chiara Casadei, Samanta Sarti, Lorenzo Cecconetto, Giandomenico Di Menna, Marita Mariotti, Roberta Maltoni, Daniela Montanari, Antonino Romeo, Ugo De Giorgi","doi":"10.1007/s10585-024-10312-3","DOIUrl":"10.1007/s10585-024-10312-3","url":null,"abstract":"<p><p>Metastatic breast cancer (MBC) is still an incurable disease, which eventually develops resistance mechanisms against systemic therapies. While most patients experience widespread disease progression during systemic treatment (ST), in some cases, progression may occur at a limited number of metastatic sites. Evidence from other malignancies suggests that local treatment with stereotactic ablative radiotherapy (SABR) of oligoprogressive disease (OPD) may allow effective disease control without the need to modify ST. Available evidence regarding local treatment of oligoprogressive breast cancer is limited, mostly consisting of retrospective studies. The only randomized data come from the randomized CURB trial, which enrolled patients with oligoprogressive disease, including both small cell lung cancer and breast cancer patients, and did not show a survival benefit from local treatment in the latter group. However, local treatment of oligoprogressive MBC is still considered in clinical practice, especially to delay the switch to more toxic STs. This review aims to identify patients who may benefit from this approach based on the current available knowledge, focusing also on the potential risks associated with the combination of radiotherapy (RT) and ST, as well as on possible future scenarios.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eva Welsch, Lilli Bonstingl, Barbara Holzer, Eva Schuster, Esther Weiß, Alexandru-Teodor Zaharie, Michael Krainer, Michael B Fischer, Amin El-Heliebi, Robert Zeillinger, Eva Obermayr
{"title":"Multi-marker analysis of circulating tumor cells in localized intermediate/high-risk and metastatic prostate cancer.","authors":"Eva Welsch, Lilli Bonstingl, Barbara Holzer, Eva Schuster, Esther Weiß, Alexandru-Teodor Zaharie, Michael Krainer, Michael B Fischer, Amin El-Heliebi, Robert Zeillinger, Eva Obermayr","doi":"10.1007/s10585-024-10313-2","DOIUrl":"https://doi.org/10.1007/s10585-024-10313-2","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) are an established prognostic marker in metastatic prostate cancer (PrC) but have received little attention in localized high-risk disease. Peripheral blood was obtained from patients with early intermediate and high-risk PrC (n = 15) at baseline, after radiotherapy, and during follow-up, as well as from metastatic PrC patients (n = 23). CTCs were enriched using the microfluidic Parsortix<sup>®</sup> technology. CTC-related marker were quantified with qPCR and RNA in-situ hybridization (ISH). Positivity and associations to clinical parameters were assessed using McNemar test, Fisher Exact test or log-rank test. The overall positivity was high in both cohorts (87.0% metastatic vs. 66.7% early at baseline). A high concordance of qPCR and RNA ISH was achieved. In metastatic PrC, PSA and PSMA were prognostic for shorter overall survival. In early PrC patients, an increase of positive transcripts per blood sample was observed from before to after radiation therapy, while a decrease of positive markers was observed during follow-up. CTC analysis using the investigated qPCR marker panel serves as tool for achieving high detection rates of PrC patient samples even in localized disease. RNA ISH offers the advantage of confirming these markers at the single cell level. Employing the clinically relevant marker PSMA, our CTC approach can be used for diagnostic purposes to screen patients profiting from PSMA-directed PET-CT or PSMA-targeted therapy.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}