Biomarker Research最新文献

{"title":"Clinical stabilization of a highly refractory acute myeloid leukaemia under individualized treatment with immune response modifying drugs by in vivo generation of dendritic cells of leukaemic origin (DCleu) and modulation of effector cells and immune escape mechanisms.","authors":"Giuliano Filippini Velázquez, Philipp Anand, Joudi Abdulmajid, Xiaojia Feng, Jan Frederic Weller, Klaus Hirschbühl, Helga Schmetzer, Christoph Schmid","doi":"10.1186/s40364-025-00817-8","DOIUrl":"10.1186/s40364-025-00817-8","url":null,"abstract":"<p><p>The conversion of leukemic blasts into antigen-presenting dendritic cells of leukemic origin (DC_leu) by GM-CSF and PGE1 has demonstrated preclinical efficacy in eliciting leukaemia-specific immune responses, offering a promising immunotherapeutic strategy for relapsed/refractory AML. We report on a 65-year-old patient with AML refractory to multiple treatment lines, including two allogeneic stem cell transplantations, who received individualized experimental treatment with intravenous GM-CSF and PGE1 and no additional anti-leukaemic therapy. Based on preceding ex-vivo treatment of patient´s blood with GM-CSF/PGE1 that showed immune activation and blast lysis, we hypothesized that intravenous administration of the compounds to the patient would promote in-vivo antileukaemic immune reactions and potentially induce clinical response. Eight treatment cycles were administered, and extensive immune monitoring was performed. The treatment was well tolerated and resulted in sustained clinical stabilization over four months. Immune monitoring showed generation of mature DC_leu, activation of leukaemia-directed effector and memory cells (including IFN-γ-producing and degranulating T and NK cells), downregulation of immune checkpoint (PD-1/CTLA-4) expressing T cells and blasts, and a reduction in regulatory B- and T cells. This case illustrates the feasibility and tolerability of GM-CSF + PGE1 therapy and its potential to modulate anti-leukaemic immunity in a patient with highly refractory AML.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"104"},"PeriodicalIF":11.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic landscape of ovarian cancer: recent advances and emerging therapies.","authors":"Ling Wang, Qun Zhang, Xue Wang, Zixuan Dong, Shanshan Liu, Qi Wang, Zhiqiang Zhang, Junji Xing","doi":"10.1186/s40364-025-00818-7","DOIUrl":"10.1186/s40364-025-00818-7","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"103"},"PeriodicalIF":11.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination immunotherapy targeting LAG-3, PD-1 and STING suppresses hepatocellular carcinoma as monitored by LAG-3 targeted PET imaging.","authors":"Zhen Quan, Yu Gao, Bo Sun, Yiwan Guo, Ziwei Jin, Na Hao, Dawei Jiang, Chuansheng Zheng, Xin Li, Quan Chen","doi":"10.1186/s40364-025-00820-z","DOIUrl":"10.1186/s40364-025-00820-z","url":null,"abstract":"<p><strong>Background: </strong>The low response rate of anti-PD-1 monoclonal antibodies (mAbs) in hepatocellular carcinoma (HCC) requires the development of combination immunotherapy strategies to improve their efficacy. This study aimed to use LAG-3-targeted PET imaging to monitor the efficacy of anti-PD-1 mAb, a stimulator of interferon genes (STING) agonist, and anti-LAG-3 mAb, both individually and in combination. Furthermore, we evaluated the potential of a triple immunotherapy regimen (anti-PD-1 mAb, STING agonist, and anti-LAG-3 mAb) to improve HCC treatment.</p><p><strong>Methods: </strong>The LAG-3 inhibitor C25 based on a cyclic peptide was chelated with NOTA, radiolabeled with [⁶⁸Ga]GaCl₃. The resulting [⁶⁸Ga]Ga-NOTA-C25 underwent in vivo PET imaging and ex vivo biodistribution examination in Hepa1-6 tumor-bearing mice. [⁶⁸Ga]Ga-NOTA-C25 PET was used to monitor the efficacy of monotherapy and dual immunotherapy with anti-PD-1 monoclonal antibody (mAb) and STING agonists. The tumor uptake of [⁶⁸Ga]Ga-NOTA-C25, tumor response, and survival rates were measured following different treatments. The therapeutic efficacy, molecular mechanisms, and safety of triple immunotherapy were validated using histopathological analysis and flow cytometry.</p><p><strong>Results: </strong>[⁶⁸Ga]Ga-NOTA-C25 PET imaging effectively and noninvasively detected LAG-3⁺ tumor-infiltrating lymphocytes (TILs) in Hepa1-6 tumor-bearing mice. In mice treated with anti-PD-1 mAb, STING agonist, or a combination immunotherapy, [⁶⁸Ga]Ga-NOTA-C25 PET revealed significantly increased LAG-3⁺ TIL levels. At the treatment endpoint, the combination of the STING agonist with the anti-PD-1 mAb resulted in a significantly higher uptake (1.35 ± 0.191%ID/g) compared to the control group (0.402 ± 0.017%ID/g), the anti-PD-1 mAb group (0.647 ± 0.037%ID/g), and the STING agonist group (0.874 ± 0.089%ID/g). Uptake of [⁶⁸Ga]Ga-NOTA-C25 was positively correlated with tumor therapeutic effects and survival rates. Triple immunotherapy with anti-PD-1 mAb, a STING agonist, and anti-LAG-3 mAb further enhanced efficacy compared to any dual immunotherapy regimen, and treatment efficacy was linearly associated with [⁶⁸Ga]Ga-NOTA-C25 tumor uptake.</p><p><strong>Conclusions: </strong>Anti-PD-1 mAb and STING agonists have shown notable synergy in upregulating LAG-3 expression on TILs in HCC, which can be successfully tracked by [⁶⁸Ga]Ga-NOTA-C25 PET imaging. Furthermore, integration of a triple immunotherapy regimen comprising an anti-PD-1 mAb, STING agonist, and anti-LAG-3 mAb demonstrated a significant improvement in therapeutic efficacy over dual immunotherapy approaches.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"102"},"PeriodicalIF":11.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of an integrative 54 biomarker-based risk identification model for multi-cancer in 42,666 individuals: a population-based prospective study to guide advanced screening strategies.","authors":"Renjia Zhao, Huangbo Yuan, Yanfeng Jiang, Zhenqiu Liu, Ruilin Chen, Shuo Wang, Linyao Lu, Ziyu Yuan, Zhixi Su, Qiye He, Kelin Xu, Tiejun Zhang, Li Jin, Ming Lu, Weimin Ye, Rui Liu, Chen Suo, Xingdong Chen","doi":"10.1186/s40364-025-00812-z","DOIUrl":"10.1186/s40364-025-00812-z","url":null,"abstract":"<p><strong>Background: </strong>Early identification of high-risk individuals is crucial for optimizing cancer screening, particularly when considering expensive and invasive methods such as multi-omics technologies and endoscopic procedures. However, developing a robust, practical multi-cancer risk prediction model that integrates diverse, multi-scale data and with proper validation remains a significant challenge.</p><p><strong>Methods: </strong>We initialized the FuSion study by recruiting 42,666 participants from Taizhou, China, with a discovery cohort (n = 16,340) and an independent validation cohort (n = 26,308) after exclusion criteria. We integrated multi-scale data from 54 blood-derived biomarkers and 26 epidemiological exposures to develop a risk prediction model for five common cancers, including lung, esophageal, liver, gastric, and colorectal cancer. Employing five supervised machine learning approaches, we used a LASSO-based feature selection strategy to identify the most informative predictors. The model was trained and internally validated in the discovery cohort, externally applied in the validation cohort, and further evaluated through a prospective clinical follow-up to assess cancer events via clinical examinations.</p><p><strong>Results: </strong>The final model comprising four key biomarkers along with age, sex, and smoking intensity, achieving an AUROC of 0.767 (95% CI: 0.723-0.814) for five-year risk prediction. High-risk individuals (17.19% of the cohort) accounted for 50.42% of incident cancer cases, with a 15.19-fold increased risk compared to the low-risk group. During follow-up of 2,863 high-risk subjects, 9.64% were newly diagnosed with cancer or precancerous lesions. Notably, cancer detection in the high-risk group was 5.02 times higher than in the low-risk group and 1.74 times higher than in the intermediate-risk group. In particular, the incidence of esophageal cancers in the high-risk group was 16.84 times that of the low-risk group.</p><p><strong>Conclusions: </strong>This is the first population-based prospective study in a large Chinese cohort that leverage multi-scale data including biomarkers for multi-cancer risk prediction. Our effective risk stratification model not only enhances early cancer detection but also lays the foundation for the targeted application of advanced screening methods, including but not limited to multi-omics technologies and endoscopy. These findings support precision prevention strategies and the optimal allocation of healthcare resources.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"101"},"PeriodicalIF":11.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients.","authors":"Tzu-Chun Cheng, Mien-Chie Hung, Lu-Hai Wang, Shih-Hsin Tu, Chih-Hsiung Wu, Yun Yen, Chi-Long Chen, Jacqueline Whang-Peng, Wen-Jui Lee, You-Cheng Liao, Yu-Ching Lee, Min-Hsiung Pan, Hui-Kuan Lin, Huey-En Tzeng, Peixuan Guo, Cheng-Ying Chu, Li-Ching Chen, Yuan-Soon Ho","doi":"10.1186/s40364-025-00819-6","DOIUrl":"10.1186/s40364-025-00819-6","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"100"},"PeriodicalIF":11.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDAC7 induction combined with standard-of-care chemotherapy provides a therapeutic advantage in t(4;11) infant B-cell acute lymphoblastic leukemia.","authors":"Oriol de Barrios, Ingrid Ocón-Gabarró, Mar Gusi-Vives, Olga Collazo, Ainara Meler, Paola A Romecín, Alba Martínez-Moreno, Juan Ramón Tejedor, Mario F Fraga, Pauline Schneider, Michela Bardini, Giovanni Cazzaniga, Rolf Marschalek, Ronald W Stam, Clara Bueno, Pablo Menéndez, Maribel Parra","doi":"10.1186/s40364-025-00810-1","DOIUrl":"10.1186/s40364-025-00810-1","url":null,"abstract":"<p><strong>Background: </strong>Infants diagnosed with B cell acute lymphoblastic leukemia (B-ALL) and t(4;11) chromosomal rearrangement display poor therapeutic response, associated to the low expression of B lymphocyte factor HDAC7. This study was conceived to identify a therapeutic strategy for t(4;11) B-ALL that restores optimal HDAC7 expression.</p><p><strong>Methods: </strong>A multiomics approach in a large infant pro-B-ALL cohort was employed to identify HDAC7's repression mechanism. These data, combined with cell culture assays in a variety of pro-B-ALL cell lines with differential HDAC7 levels, led us to define a novel combination therapy. Murine leukemia models and ex vivo assays using patient-derived xenografts (PDX) were employed to assess the benefits of this therapy when incorporated to glucocorticoid-based chemotherapy.</p><p><strong>Results: </strong>Our data demonstrates that HDAC7 is epigenetically silenced by EZH2 and KMT2A::AFF1 fusion protein. Remarkably, the Menin-1 inhibitor MI-538 restores HDAC7 expression, and the effect is enhanced by class I HDAC inhibitor chidamide. This treatment drives leukemic pro-B cells towards a more differentiated state and impairs aberrant proliferation in an HDAC7-dependent manner. This newly identified therapy increases glucocorticoid sensitivity of PDX cells ex vivo, by repressing RUNX2 transcription factor. Finally, combining MI-538 and chidamide with standard chemotherapy reduces PDX cells engraftment in vivo and delays relapse.</p><p><strong>Conclusions: </strong>The combined therapy proposed, based on Menin-1 inhibition, improves t(4;11) B-ALL cells' response to standard therapy, an effect partially mediated by HDAC7 induction. Therefore, this novel therapy opens a new field for personalized treatments in high-risk leukemia, especially for infants presenting low expression of HDAC7 B cell factor.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"99"},"PeriodicalIF":11.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple ctDNA- based biomarkers predict benefit from selective RET Inhibition in non-small cell lung cancer patients: exploratory analysis of a prospective study.","authors":"Chang Lu, Chong-Rui Xu, Yi-Chen Zhang, E-E Ke, Yue-Li Sun, Xiao-Yan Bai, Zhi-Hong Chen, Jian Su, Yu Deng, Ting Hou, Fei Zhao, Min Li, Bin-Chao Wang, Hai-Yan Tu, Zhen Wang, Xu-Chao Zhang, Hua-Jun Chen, Jin-Ji Yang, Wen-Zhao Zhong, Qing Zhou, Yi-Long Wu","doi":"10.1186/s40364-025-00809-8","DOIUrl":"10.1186/s40364-025-00809-8","url":null,"abstract":"<p><p>Selective RET inhibitors such as pralsetinib have become the standard of care for patients with RET fusion-positive non-small cell lung cancer (NSCLC). Serial analysis of circulating tumor DNA (ctDNA) has proven effective in monitoring disease control/progression and therapeutic response in NSCLC. In this prospective study, we analyzed longitudinal ctDNA profiles (at baseline, week 8, and at progression) in Chinese patients with advanced RET fusion-positive NSCLC treated with pralsetinib (NCT03037385), utilizing allele frequency-based, cfDNA quantity-normalized, and methylation-based metrics. Associations between ctDNA dynamics, tumor response, and genomic alterations were assessed. A total of 21 patients were enrolled. Baseline PIK3CA co-mutations were associated with inferior progression-free survival (PFS; 3.0 vs. 12.4 months, P < 0.001). Superior PFS was observed in patients with lower baseline ctDNA levels across all metrics: allele frequency-based (HR = 0.24; 95% confidence interval [CI], 0.07-0.80; P = 0.012), cfDNA quantity-normalized (HR = 0.20; 95% CI, 0.05-0.71; P = 0.006), and methylation-based (HR = 0.09; 95% CI, 0.01-0.85; P = 0.010). Early ctDNA clearance at the first radiographic assessment was also associated with prolonged PFS (median PFS not reached vs. 4.8 months; P = 0.002) and enhanced disease control (71.4% vs. 0%). Moreover, three distinct ctDNA dynamic profiles-clearance-rebound, reduction-rebound, and sustained clearance-were associated with different progression patterns (systemic progression, new extrathoracic lesions, new intracranial/intrathoracic lesions). No evidence of histologic transformation was identified at the time of progression. KRAS G12R and other non-canonical alterations emerged in ctDNA-rebound samples. Molecular progression preceded radiographic progression by a mean interval of 2.2 months. These findings suggest that ctDNA-based surveillance using multiple metrics, enables early forecasting of tumor response and progression in RET fusion-positive NSCLC. Early ctDNA clearance and dynamic profiles provide non-invasive biomarkers for early intervention, warranting further validation with ctDNA-guided strategies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"98"},"PeriodicalIF":9.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cells in cancer: mechanistic insights and therapeutic advances.","authors":"Jingjing Pu, Ting Liu, Yi Zhou, Mengping Chen, Xuehang Fu, Yike Wan, Junying Wang, Binzhen Chen, Amit Sharma, Veronika Lukacs-Kornek, Ingo G H Schmidt-Wolf, Jian Hou","doi":"10.1186/s40364-025-00807-w","DOIUrl":"10.1186/s40364-025-00807-w","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"97"},"PeriodicalIF":9.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computation strategies and clinical applications in neoantigen discovery towards precision cancer immunotherapy.","authors":"Zhenchang Wang, Yu Gu, Xiao Sun, Hao Huang","doi":"10.1186/s40364-025-00808-9","DOIUrl":"10.1186/s40364-025-00808-9","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"96"},"PeriodicalIF":9.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput LDI MS technology decodes the distinct metabolic landscape of prostate cancer in a large-scale cohort.","authors":"Xinrong Jiang, Chen Zhang, Jing Le, Jie Zhang, Shuo Cao, Xinran Xu, Xiaoming Chen, Sheng Cheng, Haitao Yu, Haofei Jiang, Ruichen Zang, Kunyu Wang, Weiwu Chen, Haobo Fan, Jianmin Wu, Yanlan Yu, Guoqing Ding","doi":"10.1186/s40364-025-00804-z","DOIUrl":"10.1186/s40364-025-00804-z","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"94"},"PeriodicalIF":9.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}