Published in last 50 years
Articles published on Cell Biology
- New
- Research Article
- 10.1002/advs.202508734
- Nov 7, 2025
- Advanced science (Weinheim, Baden-Wurttemberg, Germany)
- Lisa Wolff + 1 more
Matrigel is a crucial tool in cell biology, particularly for organoid research. It forms a stable scaffold with components like basement membrane proteins and growth factors, resembling the extracellular matrix and mimicking the cellular microenvironment. Its complex composition is both an asset and a drawback, as it is undefined and can vary from batch to batch. Another issue is the murine origin of Matrigel, raising ethical and scientific concerns. Interspecies variation hinders the successful translation of research findings from experimental models to clinical application in humans. Despite these well-known and often-discussed disadvantages, Matrigel is often the first choice of matrix. This review explores why Matrigel remains the gold standard for many human 3D culture systems despite its murine origin and well-known limitations. Therefore, challenges are identified that prevent researchers from transitioning to matrix alternatives and, eventually, developing completely xeno-free human model systems. To tackle these challenges, it is suggested to move beyond a one-for-all approach by pursuing a tissue- and model-specific focus when designing new matrices or selecting an alternative from already available options. To facilitate the implementation of Matrigel substitutes, we provide a matrix selection checklist and a scaffold assessment tool, and quantitative assessment criteria to evaluate matrix-model compatibility are suggested.
- New
- Research Article
- 10.1128/spectrum.01710-25
- Nov 7, 2025
- Microbiology spectrum
- Nicole L Nuckolls + 5 more
Fungi are integral to human health and well-being. They also offer scientists easy experimental systems to study facets of life shared with other eukaryotes, including humans. Most studies of fungal cell biology focus on actively growing cells, but fungi can also produce dormant cells known as spores. Spores promote fungal survival and dispersal and are often the agents of infection in pathogenic fungi. In this work, we characterize the spores produced by an easy-to-study model fungus, Schizosaccharomyces pombe. We find that the longevity and health of S. pombe spores decline over time and in response to heat stress. We characterize several traits associated with stressed and aged spores and identify parallels to aging cells in animals. This study expands the foundation for using S. pombe spores as a model system for fungal spore biology and as a model for the aging of non-dividing cells.
- New
- Research Article
- 10.1038/s41420-025-02802-4
- Nov 7, 2025
- Cell death discovery
- Zhouliang Bian + 12 more
Seminoma is the most common solid malignant tumor of the testis in young males, significantly impacting fertility. Approximately 20% of seminomas metastasize, markedly increasing recurrence risk and compromising quality of life. To investigate the poorly understood mechanisms driving seminoma metastasis, we performed a comprehensive analysis by integrating single-cell RNA sequencing, TCGA data mining, and cell biology assays. We identified significant intratumoral heterogeneity. A subset of tumor cells expressing DPPA4 and PSMA7 showed high stemness, enhanced self-renewal, and association with metastasis. Knockdown of these genes reduced sphere formation, tumor migration and proliferation in Tcam-2 and NCCIT cells. Conversely, tumor cells overexpressing PAGE5 and SAT1 exhibited reduced stemness, migratory capacity and proliferation. In the immune microenvironment, we identified IFNG+ T cells, which recruit and activate other antitumor immune cells. These cells secrete IFN-γ, which promotes tumor differentiation, reduces stemness, and mitigates tumor aggressiveness. Based on these findings, we further developed a molecular panel to aid in the identification of seminomas with a higher risk of metastasis. In conclusion, our study identifies unique molecular signatures that facilitate risk stratification based on metastatic potential, providing valuable insights for improving precision medicine.
- New
- Research Article
- 10.1158/0008-5472.can-25-4947
- Nov 6, 2025
- Cancer research
- Jessica L Chitty + 2 more
Durotaxis is the directed migration of cells along tissue stiffness gradients, and is emerging as a fundamental mechanobiological process orchestrating progression in diseases such as fibrosis and cancer. Despite compelling in vitro evidence demonstrating durotactic behaviour across multiple cell types, translating these findings to in vivo contexts has remained challenging due to the inherent complexity of isolating biomechanical cues from the myriad biochemical and architectural features that collectively define tissue properties. In their recent Nature Cell Biology study, Al-Hilal and colleagues address this translational gap through innovative bioengineering approaches combined with genetic models. Using high-resolution atomic force microscopy and intravital two-photon imaging, the authors demonstrate that pathological stiffness gradients drive fibroblast recruitment and activation in bleomycin-induced lung fibrosis, whilst simultaneously promoting quasi-mesenchymal pancreatic cancer cell dissemination. Critically, they identify the FAK-paxillin signalling axis as the mechanosensory machinery underpinning durotactic behaviour in both contexts. Pharmacological inhibition of this pathway using JP-153, or genetic disruption of tumour cell durotaxis, significantly attenuates fibrosis and metastatic burden without affecting primary tumour growth. These findings establish durotaxis as a therapeutically tractable mechanism in fibrotic and neoplastic disease, introducing a paradigm shift whereby targeting biomechanical sensing pathways may offer precise therapeutic intervention whilst preserving developmental and homeostatic processes dependent on functional mechanosensing.
- New
- Research Article
- 10.1111/joim.70036
- Nov 6, 2025
- Journal of internal medicine
- Silvia Maioli + 12 more
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline. Although amyloid-β and tau pathologies remain central to our understanding of AD, growing evidence suggests that disrupted lipid metabolism and impaired bioenergetics are closely linked to these hallmark features. Genetic, lipidomic and functional studies point to alterations in cholesterol, phospholipids and polyunsaturated fatty acids, which can influence mitochondrial function, organelle communication and glial responses. These processes are further modulated by apolipoprotein E (APOE) genotype, sex differences and systemic metabolic states such as obesity and diabetes, contributing to neuroinflammation and cognitive decline. Although findings are sometimes conflicting, an emerging theme is that lipid and energy metabolisms are central to how genetic and environmental risk factors shape AD pathogenesis. This integrated perspective highlights lipid and bioenergetic pathways as promising therapeutic targets, where metabolic modulators, lipid-directed interventions and lifestyle strategies may complement amyloid-based therapies and offer opportunities for precision approaches, particularly in women and APOE ε4 carriers.
- New
- Research Article
- 10.1210/endocr/bqaf162
- Nov 5, 2025
- Endocrinology
- Savita Dhanvantari + 1 more
Glucagon is a 29-amino acid hormone synthesized and secreted by the pancreatic alpha cell in the islets of Langerhans. It is the primary glucose counter-regulatory hormone, secreted by the alpha cell to maintain euglycemia by stimulating hepatic gluconeogenesis and glycogenolysis. In addition to glucose, the alpha cell senses and responds to a number of inputs, such as paracrine factors, neurotransmitters and other nutrients, including amino acids, to regulate the secretion of glucagon. Disruption of this fine regulation results in excessive glucagon secretion (hyperglucagonemia) and contributes to the pathogenesis of diabetes. In this mini-review, we summarize the current understanding of glucagon biosynthesis and intracellular trafficking, and discuss emerging concepts in amino acid sensing and signalling that underpin the biology of the alpha cell and that may provide clues to the control of the hyperglucagonemia of diabetes.
- New
- Research Article
- 10.1128/ecosalplus.esp-0011-2025
- Nov 5, 2025
- EcoSal Plus
- James B Kaper
EcoSal Plus (ESP) is the authoritative online review journal that publishes an ever-growing body of expert reviews covering virtually all aspects of Escherichia coli, Salmonella, and other members of the order Enterobacterales and their use as model microbes for biological explorations. This review will cover the history of ESP, starting with its origins as multi-volume printed books entitled Escherichia coli and Salmonella: Cellular and Molecular Biology that became "the Bible" for information on the physiology, metabolism, genetics, and other aspects of E. coli and Salmonella. After two printed editions, this resource moved online as EcoSal in an era when electronic publishing was still in its infancy. Progress in establishing EcoSal was slow due to technical issues of online publishing and difficulties in recruiting authors to produce new material. This venture was relaunched in 2013 as EcoSal Plus in a completely new web platform that was much more user (and author) friendly and with an expanded scope to include other members of the order Enterobacterales. EcoSal Plus will be ending as a standalone publication but will merge with Microbiology and Molecular Biology Reviews to continue providing high-quality, authoritative reviews on E. coli, Salmonella, and related organisms.
- New
- Research Article
- 10.1038/s44318-025-00626-7
- Nov 5, 2025
- The EMBO journal
- Archit Garg + 5 more
In response to various intracellular stress or damage-associated signals, inflammasomes can be activated and trigger a pyroptotic cell death process through the sequential assembly of structurally compatible and interacting filamentous oligomers involving the pyrin domains (PYD) of important inflammasome components. The PYD-containing interferon-inducible protein 16 (IFI16) has been suggested as a viral DNA sensor that can induce inflammasome formation, but it also has other inflammasome-independent functions, including interferon production. Here, the cryo-EM structure of the filament assembled by the PYD of human IFI16 reveals a helical architecture distinct from inflammasome PYD filaments. In silico interface energy calculations suggest that the helical architecture of the IFI16PYD filament prevents interactions with inflammasome PYD filaments. Biochemical and cell biology experiments consistently demonstrate that IFI16 does not directly interact with inflammasome pyrin domains. Together, our results provide insights into the structural basis of the inflammasome-independent functions of IFI16, and also show that strict architectural compatibility requirements for interactions contribute to the signal transduction specificity in inflammasome signaling.
- New
- Research Article
- 10.1007/s00441-025-04018-5
- Nov 5, 2025
- Cell and tissue research
- Yue Xi + 1 more
Kidney organoids derived from human pluripotent stem cells (hPSCs) have emerged as powerful platforms for translational nephrology, enabling complex renal pathophysiology modeling in physiologically relevant three-dimensional contexts. This review synthesizes recent advances in kidney organoid applications for disease modeling and drug discovery, highlighting their translational potential beyond developmental biology. These organoids recapitulate key human kidney architectural features, including nephron-like structures with glomeruli and tubules, while exhibiting greater cellular heterogeneity than traditional two-dimensional cultures. They effectively model monogenic renal disorders including autosomal dominant polycystic kidney disease (ADPKD), congenital nephrotic syndrome, and Alport syndrome, as well as acquired conditions like acute kidney injury and drug-induced nephrotoxicity. Kidney organoids serve as predictive nephrotoxicity screening platforms, demonstrating dose- and time-dependent responses to cisplatin, tenofovir, and aristolochic acid. However, significant challenges persist, including insufficient vascularization, developmental immaturity, segmental bias, absent urinary drainage systems, and reproducibility variability. Emerging bioengineering strategies-including endothelial co-culture, microfluidic integration, and 3D bioprinting-aim to address these limitations. Integrating stem cell biology with engineering innovations and multi-omics technologies will be crucial for refining kidney organoids into scalable, reproducible models that faithfully recapitulate human kidney physiology and disease, ultimately enabling their translation into precision medicine applications.
- New
- Research Article
- 10.3390/ijms262110753
- Nov 5, 2025
- International Journal of Molecular Sciences
- Surina Surina + 5 more
In this review we offer a guide to organ-on-chip (OoC) technologies, covering the full experimental pipeline, from organoid derivation and culture, through microfluidic device fabrication and design strategies, to perfusion systems and data acquisition with AI-assisted analysis. At each stage, we highlight both the advantages and limitations, providing a balanced perspective that aids experimental planning and decision-making. By integrating insights from stem cell biology, bioengineering, and computational analytics, this review presents a compilation of the state of the art of OoC research. It emphasizes practical considerations for experimental design, reproducibility, and functional readouts while also exploring applications in human and veterinary medicine. Furthermore, key technical challenges, standardization issues, and regulatory considerations are discussed, offering readers a clear roadmap for advancing both foundational studies and translational applications of OoC systems.
- New
- Research Article
- 10.1038/s10038-025-01425-y
- Nov 5, 2025
- Journal of human genetics
- Shinichiro Hayashi
Congenital myopathies are a group of genetically heterogeneous neuromuscular disorders characterized by early-onset hypotonia and muscle weakness. While many congenital myopathies have historically been attributed to structural defects in muscle fibers, accumulating evidence reveals that dysfunction of satellite cells-the resident stem cells essential for muscle growth and regeneration-can also cause congenital myopathy. In this review, we focus on four genes critical for satellite cell biology: PAX7, MYOD1, MEGF10, and MYMK, and discuss how pathogenic variants in these genes contribute to muscle pathology. Mutations in PAX7, a transcription factor essential for satellite cell specification and maintenance, have been identified in patients with progressive congenital myopathy and scoliosis. MYOD1 variants affect the transcriptional regulation of myogenic differentiation and have been reported in individuals with congenital muscle hypoplasia. Loss-of-function variants in MEGF10, which mediates satellite cell proliferation, result in early-onset myopathy characterized by severe weakness and areflexia. Mutations in MYMK, essential for myoblast fusion, lead to congenital myopathy with facial and axial weakness. Together, these studies illustrate that distinct steps in satellite cell function-including specification, commitment, proliferation, and fusion-are critical for normal muscle development and maintenance. Recognizing that genetic defects affecting any of these processes can lead to congenital myopathies, redefining the disease spectrum beyond purely structural muscle disorders. Expanding our understanding of satellite cell biology will be key to elucidating the full spectrum of congenital myopathies and identifying targeted therapeutic strategies.
- New
- Research Article
- 10.1073/pnas.2511042122
- Nov 4, 2025
- Proceedings of the National Academy of Sciences
- Abigail E Reeves + 10 more
The fetomaternal interface is replete with glycan-binding proteins (GBPs) that can interact with cell surface glycoprotein counterreceptors to regulate placental function. Here, we interrogate the role of galectin-3, a GBP that controls placental trophoblast syncytialization, an important differentiation process where progenitor cytotrophoblast cells fuse to produce the multinucleated syncytiotrophoblast. The molecular mechanism of galectin-3-mediated fusion has not yet been elucidated in part due to the difficulty of studying glycan-GBP binding events in live cells. To overcome these challenges, we employ a proximity labeling strategy to identify the galectin-3 interactome. From this interactome dataset, we selected and validated CD9 and integrin beta 1 as functional counterreceptors of galectin-3 and showed that CD9 is glycosylated with an N-linked glycan at a rare noncanonical sequon. Furthermore, we present evidence that galectin-3 acts to physically alter the fluidity of the cellular membrane, and it does not activate canonical syncytialization signaling pathways. Overall, we report that galectin-mediated binding events and their corresponding functions in cell biology can be precisely regulated by select glycoproteins at specific glycosites.
- New
- Research Article
- 10.1042/cs20256619
- Nov 4, 2025
- Clinical science (London, England : 1979)
- Weronika Broszkiewicz + 1 more
The relaxin family functions as pleiotropic hormones with various antioxidant, angiogenic, anti-apoptotic, anti-hypertrophic, anti-inflammatory, antifibrotic, and vasodilatory effects. To fully appreciate the potential therapeutic applications of relaxins and the pathophysiological implications, it is important to understand their multifaceted roles. This comprehensive review of current literature aims to elucidate the role of relaxins in modulating the biology and function of blood cells. It places special emphasis on the signaling pathways of relaxin family peptide receptor 1 (RXFP1) and the glucocorticoid receptor (GR) activated by relaxin-2. Relaxin-2 influences circulating blood cell counts and exerts inhibitory effects on megakaryocytes, thrombocytes, and mast cells. It also possesses immunomodulatory characteristics that affect granulocytes and agranulocytes, particularly regarding their morphology, differentiation, and function. Relaxin-1 regulates dendritic cell maturation and cytokine secretion. RXFP1 could play significant roles in blood malignancies and preeclampsia. The broad spectrum of activities demonstrated by relaxins significantly influences blood cell biology and highlights their therapeutic potential in a range of conditions, including hematological, cardiovascular, renal, pregnancy-related, and fibrotic disorders.
- New
- Research Article
- 10.1161/circ.152.suppl_3.4367452
- Nov 4, 2025
- Circulation
- Gayatri Iyer + 20 more
Introduction: The Molecular Transducers of Physical Exercise Consortium (MoTrPAC) was established to characterize the molecular basis of the health benefits of exercise. Here, we present the integrative, multi-omics response to acute endurance and resistance exercise in data derived from skeletal muscle biopsies from human participants. Methods: Sedentary participants (n=174) were randomized into endurance exercise (EE, N=64), resistance exercise (RE, N=73) or control (CON, N=37) groups. Vastus lateralis muscle biopsies were collected before a sub-maximal acute bout of either EE or RE (or CON) and at several time points after following the bout (15min, 3.5h, and 24h). Muscle biopsies were analyzed by ATACseq, RNA-seq, proteomics, phosphoproteomics, and metabolomics. Differentially abundant features at each time point were selected using false discrovery rate of 5%. Results: Multi-omics analyses revealed distinct temporal responses across omes. Maximal changes in ATAC-seq, phosphoproteome, and metabolome occurred earlier (15 min) than transcriptome and proteome changes (3.5h and 24h). Differences in the magnitude of changes were significant, with RE resulting in more altered features. Integrated multi-omics revealed early changes in differentially accessible regions (DARs; ATAC-seq) followed by mid- to late changes (3.5h and 24h) in gene and protein expression for EE and RE, suggesting temporal coordination between chromatin remodeling and gene/protein expression post-exercise. Pathway enrichment highlighted ribosomal biology and mesenchymal skeletal muscle stem cells in RE and cristae formation and mitofission at 24h in EE. Both modalities upregulated angiogenesis and VEGFR2 signaling at 15 min; this signal remained enriched 3.5h after RE but not EE. PTM analysis indicated early kinase signature enrichment, more pronounced and prolonged in RE, notably in MAPK activation. Novel findings include the downregulation of HIPK2 and HIPK3 kinase signatures, including the phosphotyrosine Y359 in HIPK3's activation loop. The leading edges of the HIPK3 signature featured two phosphosites (S173 and T285) of BAG3 as the most downregulated in both modalities, implicating the HIPK/BAG3 axis in signaling for skeletal muscle response to acute exercise. Conclusions: These MoTrPAC data provide key insights into the multi-omic exercise responses in skeletal muscle and highlight EE and RE specific effects on biological pathways.
- New
- Research Article
- 10.18502/ajmb.v17i4.20069
- Nov 4, 2025
- Avicenna Journal of Medical Biotechnology
- Majid Nimrouzi + 1 more
This study investigates the synergy between Traditional Persian Medicine (TPM)'s concept of innate heat (Hararat-e-Gharizi) and modern mitochondrial thermoregulation. TPM emphasizes innate heat as essential for sustaining life, paralleling modern understandings of mitochondrial ATP production and heat generation. This integration occurs through mitochondrial biogenesis, proton leak (via uncoupling proteins), and Reactive Oxygen Species (ROS) signaling, which correspond to the TPM concept of heat sustaining vital functions. These findings may guide novel therapeutic strategies that integrate TPM principles with mitochondrial biology. A comprehensive review of historical TPM texts and modern literature was conducted, comparing innate heat with mitochondrial roles in thermoregulation and energy balance. Data from PubMed, Google Scholar, and Scopus were analyzed to explore mechanisms of heat production in both traditional and modern contexts. Findings demonstrated that TPM's innate heat correlates with mitochondrial biogenesis, heat generation via Uncoupling Proteins (UCP1), and ROS regulation. These concepts reflect TPM’s understanding of maintaining bodily warmth for health and longevity. The relationship between Hararat-e-Gharizi and mitochondrial thermogenesis offers a bridge between ancient medicinal practices and modern cellular biology. Both emphasize the role of heat in maintaining homeostasis and preventing disease, with modern science validating TPM's holistic approach. Clarifying these mechanisms provides deeper insight into therapeutic implications, highlighting thermodynamic parallels and the role of ROS signaling as a novel framework for understanding disease etiology and treatment. This study bridges Traditional Persian Medicine and modern mitochondrial thermoregulation, introducing integrative perspectives for personalized healthcare. It also highlights thermodynamic parallels and ROS signaling as a novel framework for understanding disease etiology and treatment. This study underscores the relevance of TPM’s innate heat in modern medicine, emphasizing the importance of mitochondrial efficiency in thermoregulation and overall health. Integrating these perspectives can enhance personalized therapeutic strategies for disease prevention and longevity
- New
- Research Article
- 10.1093/genetics/iyaf237
- Nov 3, 2025
- Genetics
- Stanley Chu + 18 more
The Xenopus model organism knowledgebase, Xenbase (www.xenbase.org), bridges a wide variety of data types including genomes, anatomy, phenotypes, proteins, diseases and more. The goal of Xenbase is to support Xenopus molecular, cell and developmental biology research, to make these data available to the broader biomedical ecosystem, and accelerate the translation of Xenopus research into knowledge that will improve human health. Connections are made between data through relationships in our core data model and via a series of ontologies that serve as graph-based maps that can be traversed in various dimensions to find connections within our vast corpus of data. Data is input by a team of expert curators applying FAIR data management principles and also via automated pipelines and data processing routines. While our main focus is embryonic development and cell biology, these are often the underlying causes of compromised human health and are therefore invaluable for exploring the medical impacts of DNA sequence variants identified through patient exome or whole genome sequencing. One of the foundational elements in Xenbase with our gene-centric data structure is genomes, and we have recently vastly improved the quality of these core resources for both Xenopus laevis and Xenopus tropicalis. These and an extensive suite of other improvements are described, including updates and upgrades in content types, software and systems.
- New
- Research Article
- 10.1007/s13752-025-00512-9
- Nov 3, 2025
- Biological Theory
- Hanna Lucia Worliczek + 2 more
Abstract This article draws on and extends Bechtel’s influential work on the historical and philosophical implications of mechanistic research in cell biology. Beginning in the 1940s, cell biology relied on electron microscopy (EM) and cell fractionation, exemplifying the coupled epistemic strategies of structural decomposition and localization through experimental engagement with component parts and operations (Bechtel and Richardson [1993]2010; Bechtel 2006). In the 1970s, however, fluorescence microscopy (FM) enabled visualization of proteins and macromolecular assemblies in intact cells, which transformed mechanistic studies in cell biology. Through a historical analysis of cell adhesion and migration research, we show how the development and use of FM enabled what we call exposition of mechanisms. Instead of physically de composing cells into component parts, FM allowed researchers to visually ex pose these parts directly in their spatial-functional context in intact and even living cells . This epistemic strategy retained the mechanistic assumption that living systems can be meaningfully studied through localizable parts and operations. Yet, FM allowed for a more holistic approach to investigate structurally integrated components of minimally decomposable systems, such as focal contacts and the cytoskeleton, thus illustrating the importance of preserving the cellular context.
- New
- Research Article
- 10.1369/00221554251388501
- Nov 3, 2025
- The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
- Sharmila Ortiz + 2 more
Transmission electron microscopy (TEM) is a key tool for the ultrastructural analysis of biological samples; however, it requires optimized fixation and contrast enhancement methods to achieve accurate results. Here, we evaluated the use of tannic acid as a mordant during primary fixation for TEM processing of Giardia intestinalis and Trichomonas vaginalis. When combined with osmium tetroxide (OsO4) post-fixation, tannic acid significantly improved in-block contrast in plasma membranes, organelle boundaries, and cytoskeletal elements, while preserving structural integrity. It increased electron density without introducing artifacts and, in some cases, allowed the omission of lead citrate staining, simplifying the protocol and reducing exposure to toxic agents. Even in the absence of OsO4, samples processed with tannic acid retained sufficient contrast to visualize basal bodies, axonemes, and other cytoskeletal filaments. Moreover, tannic acid enhanced the visualization of poorly characterized structures in the transition zone. We also demonstrate its successful use as a post-staining agent, replacing uranyl acetate for ultrathin sections while maintaining high image quality. These findings support tannic acid as a safe, cost-effective, and efficient alternative to traditional contrast agents, particularly under biosafety constraints, and contribute to the improvement of TEM protocols for studying protozoan morphology and cell biology.
- New
- Research Article
- 10.3390/curroncol32110615
- Nov 3, 2025
- Current Oncology
- Piotr Remiszewski + 4 more
Mesenchymal chondrosarcoma (MCS) is characterised by small round cell biology, frequent HEY1-NCOA2 fusion, and high vascularity. These features plausibly lessen extracellular matrix barriers and confer relative chemosensitivity. We synthesised peri-operative (preoperative/neoadjuvant; postoperative/adjuvant) and palliative chemotherapy outcomes separately across multiple cohorts and case reports as well as the summarised the guidelines (ESMO/NCCN) In localised disease, integrating multi-agent Ewing-type chemotherapy with complete resection is associated with improved disease control. Contemporary 5-year overall survival (OS) typically spans ~55–73% across studies, while event-free survival (EFS) gains are demonstrated more consistently than OS gains in pooled analyses. In advanced MCS, first-line polychemotherapy yields modest, non-curative activity, with objective response rates (ORRs) of ~25–35% in adults, median progression-free survival (PFS) of ~4.7–6.7 months, and median OS of ~18 months. Activity may be higher in younger patients and for platinum–anthracycline combinations. We also discussed emerging therapies. Trabectedin demonstrates low disease control rate in translocation-related sarcomas, including few MCS cases. Anti-angiogenic tyrosine kinase inhibitors, such as apatinib and pazopanib, demonstrate activity in chondrosarcoma, but MCS-specific data are lacking. IDH1 inhibition benefits conventional subtypes rather than MCS. Early immunotherapy experience is limited, but pathway-directed strategies targeting BCL2 and PI3K-mTOR warrant evaluation.
- New
- Research Article
- 10.3389/fmed.2025.1604376
- Nov 3, 2025
- Frontiers in Medicine
- Ah-Rim Han + 7 more
Abnormalities in PBX1 represent a monogenic cause of congenital anomalies of the kidney and urinary tract (CAKUT). However, their phenotypic heterogeneity poses a challenge for timely detection, particularly in the absence of overt anomalies in the kidney and urinary tract. Here, we present a 28-year-old male diagnosed with a rare PBX1 nonsense variant identified during the evaluation of early-onset chronic kidney disease. As part of the initial workup for decreased renal function and proteinuria, a kidney biopsy was performed, revealing focal segmental glomerulosclerosis (FSGS) and acute tubular necrosis without an identifiable cause. He was initially treated with renin-angiotensin system inhibitors, followed by glucocorticoid and/or cyclosporine therapy for four years. Despite these interventions, his serum creatinine levels gradually increased without any improvement in proteinuria. Genetic testing, performed seven years after the initial visit, revealed a rare de novo heterozygous PBX1 variant, p.Arg93Ter (c.277C > T), classified as likely pathogenic. Reverse phenotyping identified cryptorchidism and dysmorphic external ears, both of which are extrarenal manifestations commonly associated with PBX1 -related CAKUT. Although this variant is predicted to be deleterious, it is flagged as escaping nonsense-mediated decay, which may explain the absence of apparent structural anomalies in the kidneys. PBX1 is prominently expressed in interstitial and endothelial cells in both fetal and adult human kidneys, and its function is not directly implicated in podocyte or tubular cell biology. Therefore, the inadvertent pathological findings in this genetic disorder may be attributed to reduced nephron endowment and/or disturbance in reciprocal cellular interactions. This case broadens the phenotypic spectrum of PBX1 -related disorders and highlights its renal manifestations, further expanding the clinical heterogeneity of FSGS.