Clinical & Experimental Metastasis最新文献

{"title":"Evaluating of radiation-induced cerebral contrast enhancements in brain metastases: analysis of incidence and risk predictors.","authors":"Kerem Tuna Tas, Abduljalil Sheirieh, Phillip Lishewski, Fatima Frosan Sheikhzadeh, Edgar Smalc, Ioanna Fragkandrea-Nixon, Khaled Elsayad, Klemens Zink, Hilke Vorwerk, Sebastian Adeberg, Ahmed Gawish","doi":"10.1007/s10585-025-10372-z","DOIUrl":"10.1007/s10585-025-10372-z","url":null,"abstract":"<p><p>Radiation-induced cerebral contrast enhancements (RICE) are frequent after photon and particularly proton radiation therapy (RT) and are associated with a significant risk for neurologic morbidity. While stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) provide high rates of local control (LC), RICE remains a significant concern that may impact patient outcomes and quality of life. This study aims to assess the incidence, risk factors, and clinical implications of RICE in patients treated with SRS or FSRT for brain metastases (BMs). A retrospective analysis was conducted on 175 patients with 330 BMs treated between October 2015 and November 2023. Median follow-up (FU) was 17 months. The incidence of RICE was determined, and potential predictive factors were evaluated using univariate Cox regression analysis. RICE was identified in 8 patients with 10 lesions (3%). Systemic therapy without immunotherapy (IT) was found to be a significant predictor of RICE (HR = 4.161,  p= 0.027). No significant association was observed between the occurrence of RICE and overall survival (OS), indicating that while RICE is a treatment-related adverse event, it does not appear to significantly influence long-term survival. RICE occurs in a small subset of patients treated with SRS or FSRT. Systemic therapy without IT significantly increases the risk, underscoring the need for careful treatment planning and patient selection. While necrosis does not impact overall survival, its potential effects on neurological function and quality of life warrant continued research into preventive and management strategies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"54"},"PeriodicalIF":3.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085047","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":"FLAIR extending beyond a quadrant (FEQ) of the cerebrum as a qualitative imaging biomarker: a conceptual proposition and proof-of-principle.","authors":"Ali A Alattar, Jiri Bartek, Carlin Chuck, Giovanni Kozel, Elaina J Wang, Hsien-Chung Chen, Parag Sanghvi, Eric T Wong, Sasmit Sarangi, Heinrich Elinzano, Sharonda Ben-Haim, Clark C Chen","doi":"10.1007/s10585-025-10370-1","DOIUrl":"10.1007/s10585-025-10370-1","url":null,"abstract":"<p><p>Significant variability exists in the use of corticosteroids for treating adverse radiation effects (ARE) after stereotactic radiosurgery (SRS) of brain metastasis (BM). Here, we determine the diagnostic utility of a quadrant-based, visual assessment of magnetic resonance (MR) FLAIR as an imaging biomarker for steroid-dependent ARE. FLAIR was assessed at four axial levels along the rostral-caudal axis of the cerebrum, defined by standard landmarks of superior temporal line, third ventricle, temporal horn, and fourth ventricle. Each axial level was divided into four quadrants, defined by 12, 3, 6, and 9 on a clock face. New, post-SRS FLAIR hyperintensity extending beyond any quadrant was defined as FEQ+. FEQ+ was then correlated with corticosteroid treatment instituted within a month of the MRI. To establish intra- and inter-rater reliability of FEQ, MR images from 20 patients (10 FEQ+ and 10 FEQ-) were assessed by three clinicians (a radiation oncologist and two neurosurgeons) for FEQ positivity. These results showed an > 85% intra- and inter-rater reliability (Cohen's Kappa and Fleiss' Kappa of 0.970 and 0.785, respectively, both p < 0.001). We tested the hypothesis that FEQ+ is associated with corticosteroid use post-SRS in an initial cohort of 40 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of FEQ for corticosteroid treatment were 75.0%, 96.4%, 75.0%, and 90.0%, respectively. To validate these findings, we examined the association of FEQ and corticosteroid use in an independent cohort of 214 SRS-treated BM patients. The sensitivity, specificity, positive predictive value, and negative predictive value of FEQ for corticosteroid treatment in this validation cohort were 94.6%, 74.0%, 43.2%, and 98.5%, respectively. We conclude that FEQ is an imaging marker with high intra- and inter-rater reliability, with a high negative predictive value (90.0-98.5%) for steroid treatment in SRS-treated BM patients. These results lay the foundation for future studies of FEQ for research and clinical applications.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"53"},"PeriodicalIF":3.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005925","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":"Survival outcomes of upfront versus delayed craniocerebral radiotherapy in EGFR-mutant NSCLC patients treated with third-generation EGFR-TKIs.","authors":"Guangchuan Deng, Yuanliang Zhou, Zhimin Wang, Jing Fan, Chenran Zhao, Jianbin Li, Zhenxiang Li","doi":"10.1007/s10585-025-10369-8","DOIUrl":"10.1007/s10585-025-10369-8","url":null,"abstract":"<p><p>We evaluated the efficacy of intervention timing of craniocerebral radiotherapy (RT) combined with third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) on prognosis of patients with EGFR mutant lung adenocarcinoma complicated with brain metastasis. In total, 348 patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations were enrolled in this retrospective study between March 2008 and September 2023. Propensity score matching (PSM) was used to adjust for demographic and clinical variables and compare survival between the EGFR-TKI plus craniocerebral RT group and the EGFR-TKI only group. Patients were categorized into upfront and delayed groups based on the timing of craniocerebral RT. Lung molGPA, overall survival (OS), and intracranial progression-free survival (iPFS) were calculated. Kaplan–Meier analysis compared iPFS and OS across groups. The 348 patients enrolled who used the third generation of EGFR-TKIs during the treatment. The median OS was 61.2 months, while the median iPFS was 15.0 months before PSM. After PSM, the median OS of EGFR-TKIs + craniocerebral radiotherapy group and EGFR-TKI alone group was 67.7 months and 48.4 months respectively (p = 0.0155). Of 206 patients who underwent craniocerebral RT, were enrolled subsequently and divided into upfront-group and delay-group showed that the median OS was 72.0 and 67.7 months respectively (p = 0.2841). For group A, the median OS of upfront-group and delay-group was 27.9 and 45.3 months, respectively (p = 0.0124). For patients in group B, there was significant difference in OS between the two groups (p = 0.0478). The median OS of the two groups was 97.7 and 70.5 months, respectively. Combining third-generation EGFR-TKIs with craniocerebral RT confers enhanced survival benefits for patients with craniocerebral metastases of EGFR-mutant lung adenocarcinoma. Upfront craniocerebral RT is recommended for patients with high lung-molGPA scores to improve both iPFS and OS.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"51"},"PeriodicalIF":3.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005957","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":"Prognostic immunotherapy score (PIS) in patients with advanced urothelial carcinoma treated with pembrolizumab: real-world data and validation from ARON-2 dataset.","authors":"Alessandro Rizzo, Anas Zayed, Elsa Vitale, Sebastiano Buti, Hideki Takeshita, Simon Crabb, Giandomenico Roviello, Emmanuel Seront, Jose Carlos Tapia, Sarah Scagliarini, Lazar Popovic, Ray Manneh Kopp, Halima Abahssain, Mimma Rizzo, Fernando Sabino Marques Monteiro, Raffaella Massafra, Oronzo Brunetti, Daniele Santini, Yüksel Ürün, Rodolfo Montironi, Veronica Mollica, Francesco Massari, Andrey Soares, Matteo Santoni","doi":"10.1007/s10585-025-10374-x","DOIUrl":"10.1007/s10585-025-10374-x","url":null,"abstract":"<p><p>Recent years have seen the development and advent of novel combinatorial strategies based on immunotherapy, and immune checkpoint inhibitor (ICI) - based treatment has established itself as a mainstay in the treatment of metastatic urothelial carcinoma (UC). Herein, we aimed to validate the prognostic value of a previously developed score, the Prognostic Immunotherapy Score (PIS), including female sex, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and liver metastases, in patients treated with pembrolizumab for advanced UC from the ARON-2 dataset. We retrospectively analyzed clinical data from Metastatic UC patients diagnosed at age ≥ 18 years. Patients progressing or recurring after platinum-based therapy were included, and treated with pembrolizumab from January 1st, 2016, to December 31st, 2023, in 68 oncological centers from 21 Countries. The Kaplan-Meier analysis was used to calculate the median follow-up. Cox proportional hazard models were used to compare the multivariable effects on patients' survival and to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A survival receiver operating characteristic (ROC) analysis was exploited in relation to OS and PFS in patients stratified by the presence of 0, 1 or ≥ 2 risk factors and OS with 0, 1 or ≥ 2 risk factors in patients stratified by age, tumor histology, site and time to metastatic disease. The comparison between subgroups was performed with the Fisher exact test. We included 1040 patients from the ARON-2 dataset. We further stratified patients based on the three previously published risk factors: female sex, ECOG-PS = 2 and liver metastases; 526 patients (51%) had 0 risk factors, 408 patients (39%) had 1 factor and 106 patients (10%) had ≥ 2 risk factors. At univariate and multivariate analyses, bone metastases, synchronous metastatic disease and our PIS model based on female sex, liver metastasis, and poor performance status were significantly associated with both OS and PFS. Our findings validate the PIS as a practical scoring model using sex, ECOG-PS, and liver metastasis to stratify survival outcomes in advanced urothelial carcinoma treated with pembrolizumab, supporting more personalized treatment decisions.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"52"},"PeriodicalIF":3.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005915","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":"Prognostic influence of chronic inflammation in patients with head and neck cancer based on sex differences.","authors":"Claudia Antwi-Boasiako, Orr Dimitstein, Sophia Chehade, Fatemeh Farshadi, Michael Hier, Marco A Mascarella, Alex Mlynarek, Moulay A Alaoui-Jamali, Sabrina Daniela da Silva","doi":"10.1007/s10585-025-10363-0","DOIUrl":"10.1007/s10585-025-10363-0","url":null,"abstract":"<p><p>Head and neck cancer (HNC) is the 7th most common cancer globally. Despite a growing interest of the impact of hormone-specific factors on cancer biology, there is limited understanding of whether the inflammatory microenvironment exhibits significant prognostic differences based on the sex of the patients with HNC. This scoping literature review evaluates if the inflammatory microenvironment exhibits significant variations between male and female patients with HNC. By compiling data from 17 datasets involving 4907patients from seven countries, we confirmed a lower incidence of HNC in females compared to males. However, only few publications addressed the specific effects of endogenous and exogenous hormones remodeling the tumor microenvironment and/or genetic predispositions. Considering sex as a biological variable, the association of various immune and blood vascular cell populations within the tumor microenvironment (including T cells, B cells, macrophages, neutrophils, and blood vessels) was validated in relation to disease progression and metastasis using The Cancer Genome Atlas (TCGA) database for head and neck cancer (Firehose Legacy, n = 528 patients). The outcome is that inflammatory factors associated with sex-specific differences influence the prognostic disparities between males and females. Delineating the molecular mechanisms involved is crucial for advancing precision medicine and tailoring treatment strategies to optimize existing therapies, ultimately improving the overall management and outcomes of HNC patients with aggressive disease.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"50"},"PeriodicalIF":3.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944890","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":"Morphological heterogeneities in prostate cancer bone metastases are related to molecular subtypes and prognosis.","authors":"Sofia Halin Bergström, Julius Semenas, Annika Nordstrand, Elin Thysell, Johan Wänman, Sead Crnalic, Anders Widmark, Camilla Thellenberg-Karlsson, Pernilla Andersson, Susanne Gidlund, Marie Lundholm, Karin Welén, Andreas Josefsson, Pernilla Wikström, Anders Bergh","doi":"10.1007/s10585-025-10365-y","DOIUrl":"10.1007/s10585-025-10365-y","url":null,"abstract":"<p><p>We previously identified three molecular subtypes of prostate cancer (PC) bone metastases, MetA-C, with MetB linked to poor prognosis after androgen deprivation therapy (ADT). This study analyzed epithelial and stromal markers using immunohistochemistry, focusing on their relationship to MetA-C subtypes, spatial heterogeneities, and clinical outcomes after ADT. High tumor proliferation and low PSA expression were associated with MetB and poor outcomes after ADT. Most metastases contained tumor epithelial subclones with different morphologies. In the metastasis stroma, blood vessels and fibroblast-like cells expressed smooth muscle actin (SMA), platelet-derived growth factor β, stroma-derived factor 1 (SDF1), periostin (POSTN), and decorin (DCN). Compared to each other, MetB metastases had higher SMA and ERG + endothelial cell densities, while MetA cases showed higher SDF1 and DCN levels. Accordingly, high POSTN and ERG + densities were associated with poor outcomes after ADT, whereas high DCN indicated favorable prognosis. Low levels of AR-positive stromal cells were linked to poor outcomes. Macrophage and T-lymphocyte densities showed no significant associations with metastases subtypes or outcome. Two stroma subtypes were identified: subtype 1 with higher bone content, lower vessel density, MetA-enrichment and better prognosis compared to subtype 2 that exhibited higher tumor proliferation and lower PSA expression. Most metastases contained regions of both stroma subtypes.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"49"},"PeriodicalIF":3.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944978","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":"MicroRNAs in the abscopal effect: bridging radiotherapy and systemic anti-tumor immunity for enhanced cancer therapy.","authors":"Fatemeh Hosseinpour-Soleimani, Amir Tajbakhsh, Zahra Salmasi, Mohammad-Taha Pirsalehi, Cambyz Irajie","doi":"10.1007/s10585-025-10364-z","DOIUrl":"10.1007/s10585-025-10364-z","url":null,"abstract":"<p><p>The abscopal effect (AE) in oncology, where localized radiation therapy (RT) triggers a systemic anti-tumor immune response, holds great promise for revolutionizing cancer treatment. Emerging evidence suggests microRNAs (miRNAs), small non-coding RNAs, are essential in mediating the intricate interactions among the tumor, immune system, and tumor microenvironment underlying the AE. miRNAs, both within the tumor and circulating as exosomal cargo, can regulate gene expression to modulate the tumor microenvironment, enhance antigen presentation, and activate anti-tumor immunity. This miRNA-mediated intercellular communication can influence the radiation response, including tumor radiosensitivity, DNA damage repair, and apoptosis. Targeting specific miRNAs or leveraging miRNA-based therapies may sensitize tumors to radiation-induced immune responses, leading to more robust and durable AEs. Understanding the epigenetic regulation of the AE by miRNAs offers novel strategies to harness this phenomenon for improved cancer outcomes. Exploring the intersection of miRNAs, radiation, and the immune system holds the promise of developing more effective, personalized radiotherapy approaches that can unleash the body's defenses against metastatic disease. Unlocking the power of miRNA-mediated signaling may be the important key to unlocking the full potential of AE in the field of cancer treatment.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"48"},"PeriodicalIF":3.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834293","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":"Targeting metabolic and epigenetic reprogramming in metastatic fumarate hydratase-deficient renal cell carcinoma.","authors":"Nadja Kührer, Irene Huebner-Resch, Roman Mayr, Abbas Agaimy, Andreas Kronbichler, Arndt Hartmann, Manuela Schmidinger, Renate Pichler","doi":"10.1007/s10585-025-10368-9","DOIUrl":"10.1007/s10585-025-10368-9","url":null,"abstract":"<p><p>Fumarate hydratase-deficient renal cell carcinoma (FHdRCC) has been classified under the new category of molecularly defined RCCs according to the WHO classification 2022. Although rare, FHdRCC is an aggressive malignancy with a high metastatic potential and poor prognosis, even at early stages. Due to its low incidence, no standard therapeutic regimen has been established to date. Several phase 2 clinical trials are evaluating combinations of targeted therapies in patients with advanced/metastatic disease. These include immune checkpoint inhibitors (nivolumab, tislelizumab, sintilimab, avelumab), multi-tyrosine kinase inhibitors (cabozantinib, erlotinib, lenvatinib, axitinib, vandetanib), and PARP inhibitors (talazoparib). The most promising combinations are nivolumab/cabozantinib (N = 5, objective response rate (ORR): 100%), lenvatinib/tislelizumab (N = 14, ORR: 93.3%), bevacizumab/erlotinib (N = 43, ORR: 72%), and sintilimab/axitinib (N = 19, ORR: 63.1%). In this review, we will provide a detailed overview of ongoing clinical trials, highlighting the roles of metabolic and epigenetic reprogramming, as well as pro- oncogenic signaling, which together form the backbone for emerging novel targeted treatment strategies. Targeting these specific signaling pathways will shift the therapeutic landscape toward personalized medicine in metastatic FHdRCC.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"47"},"PeriodicalIF":3.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798332","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":"Cold atmospheric plasma-activated liquid inhibits peritoneal metastasis in drug-resistant ovarian cancer by targeting the epithelial-mesenchymal transition.","authors":"Jinren Liu, Xiangni Wang, Yixin Cui, Jiajia Lu, Zhirou He, Yulin Xu, Rongrong Li, Guimin Xu, Lingge Gao, Xiaolin Fan, Xili Wu, Xingmin Shi, Guanjun Zhang","doi":"10.1007/s10585-025-10367-w","DOIUrl":"10.1007/s10585-025-10367-w","url":null,"abstract":"<p><p>Ovarian cancer remains a significant challenge in oncology due to its aggressive nature, late-stage diagnosis, and high rates of chemoresistance, particularly to platinum-based therapies like cisplatin. The epithelial-mesenchymal transition (EMT) is a key driver of ovarian cancer metastasis and drug resistance, highlighting the need for novel therapeutic strategies. Cold atmospheric plasma (CAP) and plasma-activated liquids (PAL), including plasma-activated medium (PAM) and saline (PAS), have emerged as promising anticancer agents, generating reactive oxygen and nitrogen species (RONS) that selectively target cancer cells. This study investigates the potential of PAL to inhibit the invasion and metastasis of cisplatin-resistant ovarian cancer cells and explores its synergistic effects with cisplatin. In vitro, PAM reduced proliferation, migration, and invasion of cisplatin-resistant ovarian cancer cells (A2780/DDP and SKOV3/DDP) while downregulating EMT-related proteins (N-cadherin, β-catenin, vimentin). H₂O₂ in PAM inhibit the PI3K/AKT/GSK3β pathway, promoting degradation of EMT regulators Snail, Slug, and β-catenin. Combining PAM with cisplatin enhanced therapeutic efficacy, reducing cell viability and metastatic potential. In vivo studies using an orthotopic mouse model further confirmed that PAS combined with low-dose cisplatin effectively suppressed tumor growth and metastasis with minimal side effects. These findings underscore the potential of PAL as an adjuvant therapy for cisplatin-resistant ovarian cancer, offering a novel approach to overcome drug resistance and inhibit metastasis. Future research should focus on optimizing treatment protocols and elucidating the molecular mechanisms underlying the synergistic effects of PAL and cisplatin.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"46"},"PeriodicalIF":3.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793611","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":"A CSF-1R inhibitor both prevents and treats triple-negative breast cancer brain metastases in hematogenous preclinical models.","authors":"Wei Zhang, Samiur Rahman, Alex M L Wu, Kristine Isanogle, Christina Robinson, Dinesh Kumar, Imran Khan, Debbie Wei, Alexandra S Zimmer, Takeo Fujii, Simone Difilippantonio, Stanley Lipkowitz, Patricia Steeg","doi":"10.1007/s10585-025-10366-x","DOIUrl":"10.1007/s10585-025-10366-x","url":null,"abstract":"<p><p>Brain metastasis is a common and serious complication of metastatic triple-negative breast cancer (TNBC) with few effective treatments. Here, we evaluated the effect of targeting the brain tumor microenvironment via the myeloid colony-stimulating factor-1 receptor (CSF-1R) pathway using the small molecule inhibitor BLZ945. Studies were conducted in two TNBC hematogenous brain-tropic models, 4T1-BR5 and 231-BR, with endpoints of prevention of brain metastasis formation and treatment of established brain metastasis. BLZ945 reduced the formation of brain metastases in both models by 57–65% (all p < 0.01) in the prevention setting. In the treatment setting, more analogous to the clinical situation, BLZ945 reduced the number and size of metastases in both models by 44–65% and 61–72%, respectively (all p < 0.05). Treatment with BLZ945 significantly reduced the number of myeloid cells in both the uninvolved brain and metastatic regions, by 15–54% across models as early as three days post-treatment. Efficacy was achieved without the need for complete suppression of brain myeloid cells, suggesting that potential adverse effects of full myeloid suppression can be minimized. Additionally, BLZ945 reduced cancer cell proliferation and astrocyte activation in the tumor microenvironment in vivo. In vitro studies showed that BLZ945 inhibited the secretion of inflammatory cytokines that stimulated cancer cell invasion; BLZ945 also indirectly reduced cancer cell proliferation through astrocyte interaction. Our findings suggest that microglial CSF-1R controls a series of myeloid regulatory pathways, both alone and in concert with other brain microenvironmental cells. The data preclinically credential CSF-1R inhibition as a potential therapeutic strategy for TNBC brain metastases.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"45"},"PeriodicalIF":3.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783633","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}