Ji Hye Shin, Ji Young Kim, Mi-Jeong Kim, Yeeun Kang, Bongkum Choi, Dohee Kwon, Yoolim Sung, Seo Hyun Kim, Ha-Jeong Lee, Chaeeun Lee, Kyeong Kyu Kim, Jae-Hyuck Shim, Duk-Hwan Kim, Eunyoung Chun, Ki-Young Lee
{"title":"USP21-EGFR-Lyn axis drives NSCLC progression and therapeutic potential of USP21 inhibition.","authors":"Ji Hye Shin, Ji Young Kim, Mi-Jeong Kim, Yeeun Kang, Bongkum Choi, Dohee Kwon, Yoolim Sung, Seo Hyun Kim, Ha-Jeong Lee, Chaeeun Lee, Kyeong Kyu Kim, Jae-Hyuck Shim, Duk-Hwan Kim, Eunyoung Chun, Ki-Young Lee","doi":"10.1186/s40364-025-00806-x","DOIUrl":"10.1186/s40364-025-00806-x","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a highly aggressive malignancy frequently driven by oncogenic mutations in the epidermal growth factor receptor (EGFR). Although EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have shown clinical efficacy, challenges such as limited response duration and intrinsic mechanisms-such as EGFR amplification-can affect therapeutic outcomes. This study investigates the role of the USP21-EGFR-Lyn axis in NSCLC progression, identifying USP21 as a key regulator of EGFR and Lyn stability. Gene Set Enrichment Analysis (GSEA) of NSCLC patient datasets revealed a strong correlation between USP21 overexpression and poor prognosis. Functional studies using USP21-knockout (USP21-KO) lung cancer cell lines demonstrated reduced proliferation, migration, colony formation, and tumor spheroid growth. Mechanistically, USP21 interacts with EGFR and Lyn, preventing their ubiquitination and degradation, thereby sustaining oncogenic signaling. In vivo, USP21 depletion significantly suppressed tumor growth in xenograft models. Additionally, pharmacological inhibition of USP21 with BAY-805 effectively reduced EGF-induced tumor spheroid formation, highlighting its therapeutic potential. Collectively, these findings position USP21 as a promising target for NSCLC treatment and offer a potential approach to complement existing EGFR-targeted therapies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"95"},"PeriodicalIF":9.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592929","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}
Fei Cai, Yufan Gu, Yingying Ling, Guanhua Yi, Shengze Zang, Tao Su, Yueqiu Liu, Ang Li, Denian Wang, Wanjun Zhao, Xinfang Xie, Guisen Li, Lunzhi Dai, Meng Gong, Hao Yang, Yang Zhao, Yong Zhang
{"title":"Proteomics in pancreatic cancer.","authors":"Fei Cai, Yufan Gu, Yingying Ling, Guanhua Yi, Shengze Zang, Tao Su, Yueqiu Liu, Ang Li, Denian Wang, Wanjun Zhao, Xinfang Xie, Guisen Li, Lunzhi Dai, Meng Gong, Hao Yang, Yang Zhao, Yong Zhang","doi":"10.1186/s40364-025-00805-y","DOIUrl":"10.1186/s40364-025-00805-y","url":null,"abstract":"<p><p>Pancreatic cancer (PC), one of the most aggressive malignancies, is characterized by a dismal prognosis owing to its low early detection rates, rapid progression, frequent postoperative complications, and limited efficacy of conventional oncological therapies. The fact that most patients are diagnosed at advanced stages underscores the critical importance of early detection for the formulation of effective treatment strategies. Despite substantial research efforts, the medical community still lacks consistent and dependable biomarkers for the diagnosis, classification, and prognosis of PC, highlighting the urgent need for innovative and more efficient approaches to identify pancreatic abnormalities at early stages. For decades, mass spectrometry (MS)-based proteomics has been extensively applied in disease diagnostics, mechanistic investigations, and screening of potential drug targets. This review systematically synthesizes recent advancements in clinical proteomic techniques and applications, highlighting significant biomarker discoveries and signal transduction networks associated with PC. By integrating these findings, we provide novel insights into the molecular mechanisms underlying PC development and progression, which may facilitate the identification of new diagnostic biomarkers and therapeutic targets for this disease.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"93"},"PeriodicalIF":9.5,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576955","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}
Benoit You, Sebastien Couraud, Philippe Ceruse, Lionel Badet, Philippe Paparel, Alice Durand, Marielle Guillet, Philippe Merle, Gaelle Lescuyer, Charles-André Philip, Francois Ducray, Mathieu Pioche, Lionel Karlin, Jean-Christophe Lifante, Olivier Glehen, Pierre-Adrien Bolze, Marion Chauvenet, Carole Langlois-Jacques, Fabien Subtil, Marie Piecyk, Aurore Carrot, Dominique Joubert, Alexandre Prieur, Berengere Vire, Sara Calattini, Lea Payen
{"title":"Diagnostic value of the wnt target and cancer-associated blood biomarker hPG80: ONCOPRO case-control prospective study.","authors":"Benoit You, Sebastien Couraud, Philippe Ceruse, Lionel Badet, Philippe Paparel, Alice Durand, Marielle Guillet, Philippe Merle, Gaelle Lescuyer, Charles-André Philip, Francois Ducray, Mathieu Pioche, Lionel Karlin, Jean-Christophe Lifante, Olivier Glehen, Pierre-Adrien Bolze, Marion Chauvenet, Carole Langlois-Jacques, Fabien Subtil, Marie Piecyk, Aurore Carrot, Dominique Joubert, Alexandre Prieur, Berengere Vire, Sara Calattini, Lea Payen","doi":"10.1186/s40364-025-00793-z","DOIUrl":"10.1186/s40364-025-00793-z","url":null,"abstract":"<p><strong>Background: </strong>hPG<sub>80</sub> (circulating progastrin), initially recognized for its oncogenic properties due to its direct link to the Wnt signaling pathway, is secreted by cancer cells and detectable in the blood of cancer patients. The ONCOPRO centralized case-control study (NCT03787056) was designed to prospectively evaluate the diagnostic utility of hPG<sub>80</sub> in patients with 16 different types of cancer.</p><p><strong>Methods: </strong>hPG<sub>80</sub> levels were measured in 421 patients with 16 newly diagnosed cancers (median age 65.6 years old) using the DxPG80.Lab kit (Biodena Care). The diagnostic performance of hPG<sub>80</sub> (the primary endpoint) was assessed by comparing baseline hPG<sub>80</sub> levels in cancer patients with those of 330 asymptomatic aged-matched healthy subjects from the general population.</p><p><strong>Results: </strong>Between 2018 and 2022, a total of 506 cancer patients were enrolled in the study, with 421 assessable across 16 distinct cancer cohorts. hPG<sub>80</sub> concentrations were significantly higher in cancer patients compared to the healthy population (median 3.8 [IQR: 1.0-11.1] vs. 1.9 [IQR: 0.6-4.2] pM, P < 0.0001). hPG80 levels were not impacted by renal failure, liver dysfunction, or cancer-associated inflammation. The diagnostic accuracy in cancer patients was ROC AUC 0.63, 95% CI = [0.59-0.67]. The highest diagnostic accuracy was seen in patients with lung cancer (AUC 0.75, 95% CI [0.68-0.82]; specificity = 88% for hPG<sub>80</sub> > 7.73 pM in patients aged > 58 years old) and hepatocellular carcinoma HCC (ROC AUC 0.75, 95% CI [0.66-083]; specificity = 88% for hPG<sub>80</sub> > 7.73 pM in patients aged > 58 years old).</p><p><strong>Conclusions: </strong>This large prospective study confirms that cancer patients have significantly higher hPG<sub>80</sub> blood concentration compared to the healthy population. Incorporating this straightforward ELISA assay into screening programs is warranted.</p><p><strong>Trial registration: </strong>NCT03787056.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"91"},"PeriodicalIF":9.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546157","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}
Jana Kotulová, Klára Baďurová, Zuzana Chyra, Sabina Ševčíková, Nikola Garbová, Tomáš Jelínek, Roman Hájek, Matouš Hrdinka
{"title":"Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.","authors":"Jana Kotulová, Klára Baďurová, Zuzana Chyra, Sabina Ševčíková, Nikola Garbová, Tomáš Jelínek, Roman Hájek, Matouš Hrdinka","doi":"10.1186/s40364-025-00799-7","DOIUrl":"10.1186/s40364-025-00799-7","url":null,"abstract":"<p><p>Multiple myeloma is a hematologic malignancy characterized by complex genetic and microenvironmental factors that drive disease progression and resistance to treatment. Despite advancements in therapies targeting established antigens, such as BCMA, CD38, SLAMF7, and GPRC5D, specific challenges persist, including antigen escape, treatment resistance, and off-tumor toxicity, highlighting the urgent need for novel therapeutic modalities. Recent advances in surface proteomics and integrative omics technologies have enabled the discovery of new surface antigens with the potential to address the challenges. By targeting antigens with higher tumor specificity and lower expression in healthy tissues, emerging immunotargets offer new avenues to minimize off-tumor toxicity and reduce the risk of relapse due to antigen loss or immune evasion. This review provides an overview of emerging immunotargets, summarizing their biological functions, roles in disease pathogenesis and immune evasion, and potential for therapeutic interventions. We focused on fifteen emerging targets currently in early clinical development or the preclinical phase, highlighting LILRB4, SEMA4A, ITGB7, CCR1, and CD70 as the most promising. These immunotargets demonstrate significant potential for next-generation immunotherapies, including antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies. Preclinical or early clinical studies show favorable safety profiles, high tumor specificity, and mechanisms to overcome immune resistance, collectively suggesting the potential for improved patient outcomes and reduced adverse effects. By presenting a comprehensive summary of these advances, this review underscores the translational potential of emerging immunotargets and provides insights to guide the development of innovative therapeutic approaches to improve outcomes for multiple myeloma patients.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"92"},"PeriodicalIF":9.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546159","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":"Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting.","authors":"Qing Zhang, Yongping Song, Keshu Zhou, Quande Lin","doi":"10.1186/s40364-025-00803-0","DOIUrl":"10.1186/s40364-025-00803-0","url":null,"abstract":"<p><p>Novel agents with innovative mechanisms of action were updated at the latest 2024 ASH Annual Meeting, some featuring first trials in combinations. Advances span new antibodies, bispecific T-cell engagers, next-generation CELMoDs, and agents targeting previously unexplored pathways in relapsed/refractory multiple myeloma. Key updates include: Cevostamab (FcRH5×CD3) demonstrated a 30.2% overall response rate in patients who underwent BCMA-targeted treatment and 60.6% in BCMA-targeted naïve patients;the triple-step dosing strategy reduced cytokine release syndrome. Lisaftoclax (APG-2575, BCL-2 inhibitor) displayed overall response rates ranging from 61.3 to 100% and ≥ VGPR rates of 32.3-100%, supporting enhanced response depth with favorable safety in combination regimens. Inobrodib (CCS1477, p300/CBP inhibitor) plus lenalidomide achieved a 71% overall response rate in pomalidomide-refractory patients, marking the first oral epigenetic modulator to reverse immunomodulatory drug resistance. Elranatamab (ELRA, BCMA×CD3) combined with carfilzomib and dexamethasone yielded an 83.3% overall response rate with a median duration of response not reached. Mezigdomide (MEZI, CELMoD) showed an 85.7% overall response rate and 17.5-month progression-free survival in Lenalidomide-refractory patients. ISB 2001 (BCMA×CD38×CD3 tri-specific antibody): achieved a 90% overall response rate at ≥ 50 µg/kg in heavily pretreated patients, with low-grade cytokine release syndrome observed. Through multi-targeted design, reversal of drug resistance mechanisms, and optimized combination strategies, treatment approaches for relapsed/refractory multiple myeloma are evolving toward greater precision, durability, and individualization.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"90"},"PeriodicalIF":9.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546158","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}
Heting Feng, Song Gong, Jiafeng Liu, Sis Aghayants, Yiling Liu, Min Wu, Yiping Wu, Jingyu Song
{"title":"Adipose-derived stem cell exosomes: mechanisms and therapeutic potentials in wound healing.","authors":"Heting Feng, Song Gong, Jiafeng Liu, Sis Aghayants, Yiling Liu, Min Wu, Yiping Wu, Jingyu Song","doi":"10.1186/s40364-025-00801-2","DOIUrl":"10.1186/s40364-025-00801-2","url":null,"abstract":"<p><p>Wound healing is a complex, multi-stage process that restores skin integrity through coordinated cellular and molecular interactions. Among the emerging therapeutic strategies, adipose-derived stem cell exosomes (ADSC-Exos) attract significant attention due to their potent regenerative capabilities. ADSC-Exos contribute to wound repair by modulating inflammatory responses, promoting cellular proliferation and migration, stimulating angiogenesis, and facilitating collagen remodeling. These exosomes carry a diverse array of bioactive molecules including cytokines, non-coding RNAs (ncRNAs), and proteins, that are delivered to target cells, thereby orchestrating the intricate processes involved in tissue regeneration. Recent advancements in exosome engineering, such as genetic modification, pharmacological preconditioning, hypoxic treatment, and incorporation with biomaterials, markedly improve the therapeutic efficacy of ADSC-Exos. This review summarizes the underlying mechanisms and therapeutic potential of ADSC-Exos in wound healing, offering new perspectives for developing exosome-based regenerative therapies. Nevertheless, challenges persist regarding the large-scale production, standardized isolation, and clinical translation of ADSC-Exos. Future research should aim to enhance exosome yield and purity, elucidate the mechanisms governing exosome biogenesis, and validate their clinical efficacy through well-designed trials.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"88"},"PeriodicalIF":9.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337242","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}
Nan-Nan Wang, Fei Cao, Lin-Han Zhang, Yi-Fei Zheng, Da Xu
{"title":"Multi-omics: a bridge connecting genotype and phenotype for epilepsy?","authors":"Nan-Nan Wang, Fei Cao, Lin-Han Zhang, Yi-Fei Zheng, Da Xu","doi":"10.1186/s40364-025-00798-8","DOIUrl":"10.1186/s40364-025-00798-8","url":null,"abstract":"<p><p>Epilepsy is a collection of neurological disorders characterized by abnormal neuronal discharges, resulting in spontaneous and recurrent unprovoked seizures. Despite the use of over 20 anti-seizure drugs, conventional one-size-fits-all approaches are insufficient to meet the needs of all patients, and about 1/3 patients developed drug-resistant epilepsy. Recently, the establishment of precision medicine-based clinical management for epilepsy may bring new insights, especially omics-based approaches. Single omics approach is limited to addressing questions from a single molecular perspective. Whereas multi-omics approaches enable a comprehensive characterization of multiple molecules, revealing the complex molecular dysregulation networks underlying different epilepsy phenotypes. Furthermore, multi-omics methods have catalyzed a paradigm shift in scientific inquiry, transitioning from traditional hypothesis-driven types to data-driven research architectures. Despite the full potential of multi-omics research yet to be realized, its application in epilepsy holds great promise, from the discovery of epileptic biomarkers to personalized management. In this review, we performed a comprehensive overview of the omics technologies and multi-omics integration strategies, followed by an exploration of their role in enhancing the management of epilepsy treatment and care, hoping to provide new directions for future researches.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"86"},"PeriodicalIF":9.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327743","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}