Search Results (320)

Kaempferol is a natural flavonol compound widely present in various single-herb remedies and compound formulations used for the treatment of ocular diseases. Despite its inherent pharmaceutical limitations, accumulating evidence indicates that kaempferol exerts broad protective effects against diverse ocular disorders through multiple biological pathways, highlighting its potential as a multi-target therapeutic candidate in ophthalmology. However, current evidence regarding kaempferol-based ophthalmic applications remains fragmented across different ocular diseases and mechanistic investigations, and a comprehensive evaluation of its therapeutic potential, translational challenges, and existing limitations is still lacking. This review systematically summarizes the research progress on kaempferol in the treatment of eye diseases, encompassing its source distribution, structural characteristics, ocular delivery strategies, disease spectrum coverage, molecular mechanisms, and safety profile. By critically evaluating currently available evidence, this review further identifies unresolved issues and translational barriers that hinder the clinical application of kaempferol in ophthalmology. Regarding delivery strategies, carriers such as gelatin nanoparticles, porous bovine serum albumin membranes, platelet-derived extracellular vesicles, and polyvinylpyrrolidone-based nanocomposites have preliminarily improved ocular surface retention and corneal permeability of kaempferol in models of corneal neovascularization and alkali burns. In terms of therapeutic indications, kaempferol has demonstrated protective effects in diverse experimental models, including age-related macular degeneration (AMD), diabetic retinopathy, diabetic cataract, dry eye disease, fungal keratitis, corneal transplant rejection, acute glaucoma, and retinoblastoma. At the mechanistic level, kaempferol exerts comprehensive pharmacological actions—anti-inflammatory, antioxidant, metabolic regulation, anti-angiogenic, and immunomodulatory—by modulating multiple signaling pathways, including MAPK, NF-κB, STAT1/IRF7, Nrf2/HO-1, VEGF/PI3K/Src/Akt/ERK, aldose reductase, estrogen-related receptor alpha (ERRα), and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Available safety assessments suggest that kaempferol exhibits a generally favorable safety profile across ocular, cellular, systemic, and genetic evaluations. Despite these advances, the clinical translation of kaempferol in ophthalmology remains limited by insufficient clinical and pharmacokinetic evidence, underdeveloped targeted delivery strategies, and a lack of integrated understanding of its molecular basis in ocular protection. By systematically integrating evidence from ocular disease models, molecular mechanisms, delivery strategies, and safety evaluations, this review bridges fragmented knowledge regarding kaempferol-based ophthalmic applications and provides an integrated framework for understanding its therapeutic potential and translational prospects. Overall, this review highlights kaempferol as a promising multi-target therapeutic candidate for ocular diseases and provides insights into its future translational development. Full article

Traditional inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have long been characterized as classical antiproliferative agents that induce G1 cell cycle arrest by blocking the phosphorylation of the retinoblastoma protein (Rb). However, recent studies in lung cancer have expanded this paradigm, revealing a functional transition from exclusive tumor suppression to the profound remodeling of the tumor microenvironment (TME) to enhance antitumor immunity. This review systematically outlines the genomic aberrations of the CDK4/6-Rb axis across lung cancer subtypes and dissects its immunomodulatory networks. These encompass the activation of effector T cells, the alleviation of immunosuppression mediated by regulatory T cells (Tregs), and the enhancement of antigen presentation via the Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. Furthermore, we analyze acquired resistance mechanisms, primarily focusing on p21-CDK2 bypass activation mediated by Cyclin E1 gene (CCNE1) amplification and tumor protein 53 gene (TP53) mutations. We also review clinical investigations combining CDK4/6 inhibitors with targeted therapies against driver genes, as well as immune checkpoint inhibitors in lung cancer. Notably, in the context of lung cancer, these combinatorial strategies have been primarily investigated in the second-line or subsequent settings following progression on standard platinum-based chemotherapy or immunotherapy. Finally, we propose individualized, stratified treatment strategies based on genomic and immunological biomarkers, providing a translational framework for overcoming multidrug resistance and optimizing next-generation combinatorial regimens in lung cancer. Full article

Background/Objectives: Artificial intelligence (AI) is increasingly being evaluated for ophthalmic diagnosis, screening, and triage, yet its role in paediatric eye care remains less established than in adult ophthalmology. This systematic review aimed to synthesise evidence on AI-enabled tools for paediatric ophthalmic diagnosis, screening, triage, surveillance, and referral, with an emphasis on diagnostic performance, safety, workflow integration, equity, and implementation readiness in primary, community, and primary care-relevant settings. Methods: A PRISMA-guided systematic review was conducted using MEDLINE, Embase, Web of Science, Scopus, and IEEE Xplore from inception to 30 March 2026. Eligible studies evaluated AI or machine-learning tools for children and adolescents aged 0–18 years in relation to paediatric eye conditions. Study selection and data extraction were undertaken independently by reviewers, with disagreements resolved by consensus or third-reviewer adjudication. Methodological and reporting quality was evaluated using an author-adapted six-domain rubric informed by APPRAISE-AI. Diagnostic-accuracy studies were assessed using an author-adapted QUADAS-2 framework incorporating QUADAS-AI-informed AI-specific considerations, the prediction-model study was assessed using PROBAST+AI, and the non-randomised treatment-effect study was assessed using ROBINS-I. The public dataset descriptor was evaluated separately using an author-developed dataset-quality, representativeness, and applicability framework. Because of clinical and methodological heterogeneity, findings were synthesised thematically. Results: Twelve empirical studies and one public dataset descriptor were included, covering retinopathy of prematurity, retinoblastoma, amblyopia risk, myopia, congenital cataract, and visual-acuity assessment. AI systems frequently demonstrated promising diagnostic or screening performance, including sensitivity-first detection of treatment-requiring retinopathy of prematurity, high discrimination for retinoblastoma activity, and strong myopia prediction using fundus images. Several studies supported feasibility in neonatal, school, and community workflows using smartphone-based imaging, task-shifted operators, tele-referral, and human-in-the-loop review. However, external and temporal validation, calibration, patient-level reporting, subgroup and fairness assessment, and economic evaluation were limited. Conclusions: AI-enabled tools show promise for supporting selected paediatric ophthalmic screening, triage, and surveillance pathways, particularly when combined with image-quality control, explicit escalation, and human oversight. However, confidence in the reported performance is limited by single-centre studies and enriched samples, small numbers of clinically important cases, heterogeneous analytical units, potentially optimistic aggregation procedures, limited external or temporal validation, incomplete calibration, and absent fairness analyses. Routine autonomous implementation remains premature. Full article

Small cell carcinoma of the cervix (SCCC) is a rare yet highly aggressive subtype of cervical cancer (CC), characterized by early invasion, high metastatic potential, frequent recurrence, and extremely poor prognosis, which severely impairs women’s physical and mental health. Currently, high-risk human papillomavirus (hr-HPV, particularly HPV18) infection is recognized as one of the core drivers underlying the initiation and progression of SCCC. Malignant evolution is not triggered by a single infection event but is cooperatively regulated at multiple molecular levels, including HPV genome integration, critical gene mutations, and aberrant activation of multiple signaling pathways. In addition, SCCC exhibits an HPV-independent oncogenic pathway mainly mediated by somatic mutations in tumor protein 53 (TP53) and retinoblastoma 1 (RB1), thus forming a dual pathogenic mechanism. Based on current clinical understanding and molecular mechanisms, this paper reviews the molecular pathogenesis and subtypes of SCCC, reveals the associations between tumor heterogeneity, therapeutic resistance, and metastasis, and proposes potential novel targets for the treatment of SCCC. This study innovatively presents a closed-loop model of two-way empowerment between basic research and clinical application. It emphasizes that basic research should be oriented toward real clinical problems and highlights the reciprocal feedback of clinical practice on basic research, thereby achieving dynamic iteration and collaborative breakthroughs in both fields. Full article

Background: PRMT5, or protein arginine methyltransferase 5, is recognized as an epigenetic regulator that suppresses gene transcription through symmetric dimethylation of histone arginine residues, including histone H4 arginine 3 (H4R3me2s) and histone H3 arginine 8 (H3R8me2s), modifications associated with chromatin condensation and transcriptional repression. PRMT5-mediated methylation has been associated with recruitment of polycomb repressive complex 2 (PRC2) and enhancer of zeste homolog 2 (EZH2)-mediated H3K27me3 deposition, contributing to stable repression of tumor suppressor genes and apoptosis-related effectors in breast cancer. Methods: The molecular and functional impacts of PRMT5 inhibition were studied in TNBC cell lines with a pharmacological inhibitor (CMP5). Cellular responses were evaluated using a viability assay, qPCR, Western blotting, Annexin V/PI staining, and transwell migration/proliferation assays. Results: PRMT5 inhibition substantially reduced TNBC viability in a time- and dose-dependent manner. EZH2 was downregulated, whereas the tumor suppressor retinoblastoma-like protein 2 (RBL2) was induced, concomitant with low expression of Cyclin D1. These changes were accompanied by upregulation of pro-apoptotic effectors (Caspase-3, Caspase-10, death-associated protein 1 (DAP1), and BCL2-associated x protein (BAX) and repression of the pro-survival B-cell lymphoma 2 (BCL2), consistent with apoptosis-associated molecular responses. Functionally, CMP5 treatment was associated with reduced migratory behavior in TNBC cells under the experimental conditions tested. Conclusions: These findings suggest that PRMT5 inhibition by CMP5 is associated with reduced TNBC cell viability, impaired migration, increased expression of apoptosis-associated regulators and enhanced apoptotic cell death as measured by Annexin V/PI analysis in vitro. Further mechanistic and in vivo studies are required to clarify the therapeutic relevance of PRMT5 inhibition in TNBC. Full article

Cancer predisposition syndromes (CPSs) account for 8.5–18% of all childhood cancer cases. Most of them are inherited in an autosomal dominant pattern; consequently, there is a 50% risk of transmission to offspring. Early detection of CPSs is crucial for choosing patient treatment strategies and for counseling in the family. This study enrolled 886 pediatric patients with hematologic and solid neoplasms from prospective and retrospective cohorts (2018–2025). Clinical exome or multigene panel sequencing was used to analyze blood DNA. Overall, 186 pathogenic/likely pathogenic (PLP) variants in cancer-associated genes were identified in 176/886 (20%) of patients, and the most frequently mutated were the NF1 (n = 35) and TP53 (n = 18) genes. Among the 186 PLP variants, 126/886 (14.2%) were causative for pediatric neoplasms, while 56/886 (6.3%) were heterozygous mutations associated with adult-onset CPSs affecting DNA repair. The highest total mutation rate was revealed in retinoblastoma (80%), peripheral nerve sheath tumors (60%), and pheochromocytoma/paraganglioma (47%), while the lowest rate was found in hematologic malignancies (4.6%) and neuroblastoma (12%). The wide range and high frequency of deleterious variants in pediatric patients, especially in those with solid tumors, highlights the importance of multigene panel sequencing for the accurate determination of CPSs. Full article

Background: Retinoblastoma (RB) is a rare pediatric malignancy characterized by small sample sizes and low event rates, where conventional association-driven feature selection may lead to unstable models, overadjustment, and limited generalizability. However, existing survival prediction studies lack a careful treatment of feature selection that accounts for underlying causal structure. Objectives: To develop and validate a causality-guided machine learning model for RB survival prediction by jointly incorporating survival time and survival status as outcome variables. Methods: We analyzed 1015 RB patients from the SEER database (1975–2020). A causality-informed feature selection framework was developed to address the challenges of rare-disease data. Specifically, candidate variables were evaluated through a three-step evidence-integration process: (1) univariate Cox proportional hazards (CPH) analysis for initial statistical screening; (2) causal structure learning using the PC algorithm on the variables retained from Step 1 to construct a directed acyclic graph (DAG) and exclude structurally inappropriate variables (colliders or descendants of the outcome); and (3) LASSO-based feature screening performed independently on the full set of candidate variables. The final features were obtained by taking the intersection of the variables retained from Step 2 and Step 3. Survival models were then trained using the selected features, with model comparison performed as a secondary step. Results: The proposed framework consistently identified four structurally and prognostically robust predictors—laterality, “SEER historic stage A”, “RX Summ”, and sequence number—through this evidence-integration process. Compared with conventional approaches, the causality-informed framework reduced the feature set while improving model stability and interpretability. Notably, compared with LASSO-only selection, which retained a larger set of variables, the causality-informed approach yielded a more parsimonious feature set with improved predictive performance, suggesting reduced overfitting in a low-event setting. Survival models trained on this refined feature set demonstrated reliable predictive performance, with the random survival forest achieving the highest discrimination (C-index = 0.739). Importantly, the selected predictors aligned with clinically plausible pathways in the learned DAG, supporting their causal relevance. Conclusions: This study demonstrates that incorporating causal structure into feature selection provides a more reliable and interpretable foundation for survival modeling in retinoblastoma. Rather than focusing on algorithmic comparison alone, our findings highlight that careful, causality-informed feature selection is critical for improving robustness in rare-disease prediction tasks. This framework may serve as a generalizable methodological template for other rare clinical settings prone to spurious associations. Full article

Pharmacological cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have reshaped the treatment landscape of HR-positive, HER2-negative (HR+/HER2−) breast cancer and are increasingly being explored across diverse malignancies. By preventing retinoblastoma (RB) phosphorylation and enforcing G1-S cell cycle arrest, these agents achieve durable tumour control with a more favourable toxicity profile than conventional chemotherapy. Beyond their canonical cytostatic effects, prolonged CDK4/6 inhibitor treatments induce cellular senescence, a stable, proliferative arrest accompanied by profound transcriptional, epigenetic, and secretory changes. This review summarises current knowledge on CDK4/6 inhibitor-induced senescence in both cancer and normal cells as a central biological mechanism that links tumour suppression and microenvironmental remodelling. Importantly, this process is highly context-dependent, differing between tumour and non-malignant cells, with a distinct senescence-associated secretory phenotype (SASP) that shapes immune responses and tissue homeostasis. We also discuss how CDK4/6 inhibitor-induced senescence influences the tumour microenvironment by modulating immune surveillance, stromal interactions, and cancer cell plasticity. Finally, we examine emerging resistance mechanisms and rational combination strategies for CDK4/6 inhibitors, including targeting compensatory signalling pathways, immune checkpoint blockades, and senescence-directed sequential therapies. Collectively, CDK4/6 inhibitor-induced senescence represents both a challenge and a therapeutic opportunity, underscoring the need to integrate cell cycle control with the modulation of cellular states. Full article

Background: Cerebrovascular accidents (CVAs) are among the most serious complications of intra-arterial chemotherapy (IAC) for retinoblastoma (RB). This study evaluated the incidence and potential risk factors of this rare event. Methods: A retrospective cohort study included RB patients who received IAC at a tertiary cancer center. Diagnosis of CVAs was based on clinical and/or neuroimaging findings. Data included demographics, tumor features, complications, and outcomes. Meta-analysis was not feasible due to heterogeneity. A systematic review following PRISMA guidelines was conducted across major databases up to December 2025, including studies reporting CVA after IAC. Results: The cohort included 33 children who underwent 104 IAC procedures (Melphalan). CVA occurred in three patients (3/33 (9%) of patients, and 3/104 (2.9%) of procedures). Two were confirmed by neuroimaging, while one was a transient ischemic attack. Two patients (67%) were girls, and 2 of 3 (67%) were younger than 1 year. All events occurred during the IAC procedure and were ipsilateral to the treated eye. Two patients had no residual neurological deficits, while one showed improvement with only a minor residual deficit. The systematic review included 14 studies with 932 patients and identified 11 CVA events (1.2%; Range 0–9.1% per patient and 0–2.2% per IAC procedure). All were ischemic with variable presentations. Younger age, repeated catheterization, vasospasm, and embolic events were common risk factors. Outcomes were generally favorable. Conclusions: CVA after IAC, though rare, may be underreported. Events are likely procedure-related and influenced by age, treatment intensity, and vascular toxicity. Careful technique, close monitoring, and standardized reporting are needed to recognize/reduce the real risk. Full article

Protein arginine methyltransferase 5 (PRMT5) mediates arginine methylation of a wide range of proteins and plays context-dependent oncogenic or tumor-suppressive roles. In cancer, PRMT5 represses several tumor suppressor genes, including E-cadherin, TP53BP1, ST7, PTEN, and RB (retinoblastoma). Elevated PRMT5 expression has been reported across multiple cancer types, notably triple-negative breast cancer (TNBC). In TNBC, high PRMT5 levels are associated with enhanced cancer stem cell self-renewal, increased tumor growth and metastasis, and reduced patient survival. Mechanistically, PRMT5 promotes breast cancer stem cell maintenance and proliferation through stabilization of the transcription factors KLF4 and KLF5. Disruption of the PRMT5–KLF4 axis results in significant tumor reduction in TNBC models. Moreover, increased PRMT5 expression has been linked to resistance to chemotherapy and immunotherapy in TNBC. Notably, PRMT5 inhibitors demonstrate synergistic anticancer activity when combined with inhibitors of key oncogenic signaling pathways, including EGFR, PARP, and AKT. While several PRMT5 inhibitors are currently being evaluated in clinical trials for other malignancies, no clinical trials have yet been initiated specifically for TNBC. Full article

Objective: To provide a comprehensive literature review of original work on artificial intelligence in ocular oncology. Methods: Scoping review of PubMed-indexed original articles (n = 94) on the use of artificial intelligence in ocular oncology, retrieved during the month of February 2026 and independently screened by two ocular oncologists. Results: Most of the literature on artificial intelligence (AI) in ocular oncology focuses on uveal melanoma and its differentials (n = 39, 41%), followed by retinoblastoma (n = 14, 15%) and orbital tumors (n = 12, 13%). The purpose of using the AI models was to screen, diagnose, and classify the disease (n = 59, 62%) and to treat, predict outcomes, and monitor the disease (n = 35, 37%). Most literature (n = 32, 34%) on AI in ocular oncology originates from China. Datasets comprised images in 78% (n = 73) of the studies, clinical parameters in 14% (n = 13), and omics data in 12% (n = 11). Most studies worked on developing AI models (n = 83, 88%), of which two reached a deployment stage. Few studies evaluated or incorporated pre-existing models (n = 11, 12%). Supervised learning strategy was most commonly employed (n = 75, 80%). Among studies that developed AI models, traditional machine learning architectures were used in 36, deep learning in 39, and a combination in 8. Most studies (n = 59, 63%) were at a Clinical AI Readiness Evaluator Technology Readiness Level 4, i.e., at the prototype development stage. Conclusions: Despite the limitation of a single database search, a surge in AI applications in ocular oncology after 2020 is evident. Most studies are in the model development stage, and few have been deployed in the real world for clinical implementation. Very few models have proven effective in real-world clinics and the community, holding promise for the future. Full article

Retinoblastoma (RB) is the most common intraocular malignancy of childhood, yet molecular assessment of disease dissemination and minimal residual disease (MRD) remains challenging due to the contraindication of intraocular biopsy. Here, we evaluate the feasibility of cell-free RNA (cfRNA)- and circulating tumor cell RNA (ctcRNA)-based liquid biopsy for the sensitive detection of disseminated retinoblastoma using digital PCR (dPCR) targeting the retina-specific markers CRX and RBP3. We analyzed 433 bone marrow (BM), peripheral blood (PB) and cerebrospinal fluid (CSF) samples collected longitudinally from 50 patients with RB. dPCR assays demonstrated high analytical sensitivity. cfRNA detection showed complete sensitivity and negative predictive value in bone marrow compared with myelogram analysis, frequently identifying molecular positivity in cytologically negative samples. In cerebrospinal fluid, cfRNA detection was highly specific but less sensitive, reflecting compartment-specific biological constraints. Longitudinal analysis revealed that changes in CRX and RBP3 ctcRNA levels closely tracked treatment response, preceded cytological evidence of bone marrow involvement in several cases, and identified molecular persistence or re-emergence during follow-up, including after hematopoietic stem cell transplantation. Together, these findings demonstrate that cfRNA- and ctcRNA-based liquid biopsy using CRX and RBP3 enables sensitive and dynamic detection of disseminated retinoblastoma, particularly in bone marrow, and supports its potential utility for MRD monitoring. Longitudinal patient analyses will be required to define prognostic thresholds and establish the clinical role of this approach in risk stratification and long-term surveillance. Full article

The overexpression of cyclin-dependent kinase inhibitor p16 (INK4a) is widely recognized as a surrogate marker for high-risk human papillomavirus (HPV) in anogenital malignancies, but its significance in invasive breast carcinoma is complex and remains frequently debated. While historically investigated as a viral proxy, emerging evidence suggests that elevated p16 levels in breast tissue may instead reflect intrinsic cell-cycle dysregulation and retinoblastoma (Rb) pathway disruption, though direct molecular confirmation is lacking in this area of research. This study aims to evaluate the role of p16 as an indicator of tumor aggressiveness for high-risk phenotypes. We conducted a retrospective study of 100 female patients with invasive breast carcinoma. Employing a purposive sampling strategy rather than a consecutive series, we analyzed a targeted cohort consisting predominantly of triple-negative breast cancer (TNBC) and high-grade tumors to evaluate biomarker patterns specifically in advanced disease contexts. Immunohistochemical assessment was performed using a standardized cumulative nuclear and cytoplasmic scoring system, with expression thresholds defined by receiver operating characteristic (ROC) curve analysis optimized for histological grade. p16 overexpression was a predominant characteristic of these aggressive tumors and was identified in 68% of cases. Statistical evaluation revealed a robust and significant correlation between p16 overexpression and the triple-negative molecular subtype, as well as a marked inverse relationship with estrogen receptor (ER) status. Although p16 levels were frequently associated with specific aggressive phenotypes, no statistically significant difference in overall survival was observed between expression groups, a finding attributable to the uniformly high-risk nature of the selected cohort. This study suggests an association between p16 expression levels and aggressive tumor features, although the study design limits causal inferences. A non-significant trend towards p16 overexpression was observed in ductal carcinomas compared to lobular subtypes, while high p16 expression was noted exclusively in G3 tumors within this selected cohort, a finding influenced by the purposive sampling strategy and the ROC-based cutoff definition. Tumor necrosis was more prevalent in p16-overexpressing tumors. Furthermore, p16 levels showed a strong inverse relationship with estrogen receptor (ER) status, as they were significantly elevated in ER-negative and triple-negative tumors compared to luminal phenotypes. Full article

Retinoblastoma is the most common intraocular malignancy of childhood and is most often driven by loss of the RB1 tumor suppressor gene. While current treatments achieve high survival rates, they are frequently associated with significant morbidity, highlighting the need for more precise, biology-driven therapeutic methods. Increasing evidence suggests that retinoblastoma progression is not dictated by neoplastic cells alone, but rather by complex interactions within the tumor microenvironment, including stromal and immune components. In this review, we examine the cellular and molecular landscape of retinoblastoma with a particular focus on the immune microenvironment, including the spatial distribution and functional roles of innate and adaptive immune cells, as well as immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4. We discuss how tumor- and treatment-induced immune suppression shapes disease progression and therapeutic response, and how chemotherapy alters immune infiltration and checkpoint expression. Finally, we explore emerging immunotherapeutic and cell-based approaches, emphasizing the potential for combination therapies that integrate immune modulation to improve outcomes and reduce long-term toxicity in retinoblastoma. Full article

Ovarian cancer remains the most lethal gynecologic malignancy, with the majority of patients presenting at advanced stages and exhibiting poor long-term survival. High-grade serous carcinoma (HGSC), the predominant subtype, likely originates from fallopian tube epithelial cells (FTECs), whose biology is strongly influenced by hormonal signaling. Progesterone receptor (PR) expression, particularly of the PR-B isoform, is associated with improved prognosis in HGSC; however, the isoform-specific molecular mechanisms in precancerous FTECs remain unclear. This study investigated the distinct biological and transcriptomic effects of PR-A and PR-B in p53- and Rb-defective FE25 FTEC-derived cells. Stable overexpression of PR-A suppressed cell proliferation, enhanced apoptosis, and induced robust senescence, whereas PR-B promoted proliferation and activated JNK/c-Jun signaling. Upon progesterone (P4) treatment, both isoforms mediated cell-cycle arrest and apoptosis, with PR-A exhibiting stronger Sub-G1 induction. PR-A and PR-B differentially regulated cell-cycle inhibitors, senescence markers, and downstream pathways, including the PI3K–Akt and MAPK pathways, while RNA sequencing analyses revealed broader P4-induced transcriptomic changes in PR-B than in PR-A, involving immune, angiogenic, and proliferative programs. Collectively, these findings demonstrate that PR-A and PR-B exert distinct yet complementary regulatory roles in FTEC biology and progesterone responsiveness. The observed PR isoform-dependent effects in FE25 cells should be interpreted as context-specific mechanistic insights rather than direct predictors of clinical prognosis or treatment response. Full article