Search Results (3,237)

Computational clearing (CC) enhances widefield (WF) fluorescence microscopy by suppressing out-of-focus haze and autofluorescence, yielding semi-confocal quality images suitable for segmentation and image-based phenotyping. Here, we propose an “image tracing” workflow for inflammatory mouse intestinal organoids (mIOs) using paired CC and WF images to generate a differential signal (CC − WF). mIOs were derived from intestinal crypts of Lgr5-EGFP stem cell reporter mice and expanded under epidermal growth factor, Noggin, and R-spondin (ENR) conditions. Inflammation was induced by dextran sulfate sodium (DSS) treatment. CC processing enhanced phalloidin-stained apical F-actin and improved EGFP signals by reducing background noise, enabling robust segmentation and quantitative extraction of image morphometrics including area, circularity, and perimeter. CC-WF vectors derived from three-dimensional area–perimeter–circularity plots sensitively captured DSS-induced epithelial disruption analogous to a leaky-epithelium phenotype. Transcriptomic analysis by RNA-seq of DSS-treated mIOs revealed upregulation of inflammatory pathways including TNF-α signaling via NF-κB and IL-6/JAK/STAT3, aligning with microscopy findings. In a proof-of-concept demonstration using phalloidin-stained fluorescence images, ROC analysis of the CC-WF workflow achieved an AUC = 0.95 with 87.5% sensitivity and 92.9% specificity in distinguishing intact from injured mIOs. Full article

Background: Abemaciclib (ABM) in combination with tamoxifen (TAM) is an extremely significant treatment regimen for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. It is approved for patients to reduce the risk of cancer recurrence. A bioanalytical method for the simultaneous determination of this new anti-breast cancer combination and its pharmacokinetic application has not yet been reported. Methods: An ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed for quantifying ABM, TAM, and its metabolites, including abemaciclib active metabolites M2, M18, and M20 and tamoxifen active metabolite N-desmethyl tamoxifen (NDTAM), in rat plasma using econazole as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 column (100 × 2.1 mm ID, 2.6 µm) using gradient elution with 5 mM ammonium formate in water (eluent A) and 5 mM ammonium formate in water/methanol (1:9, v/v, eluent B) at a flow rate of 0.4 mL/min. Detection was performed on a TSQ Fortis Plus mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. Results: The developed method was validated according to the guidance of the FDA. Linearity in rat plasma (ng/mL) was achieved from 1 to 1000 for ABM, TAM, and M20; 3 to 1000 for M2; 5 to 500 for M18; and 1 to 500 for NDTAM; with correlation coefficients ranging from 0.9991 to 0.9931 for all analytes using a weighting factor of 1/X². The lower limit of detection (LLOD) ranged between 0.3 and 1.5 ng/mL for all drugs. The accuracy ranged from 96 to 108% and the precision was less than 7.6% RSD for all analytes. For the first time, the newly developed approach was effectively used in a pharmacokinetic study on the simultaneous oral administration of ABM and TAM in rats that received 30.0 mg/kg of ABM and 8.0 mg/kg of TAM. Conclusions: To the best of our knowledge, this is the first reported UPLC–MS/MS method for the assay of ABM, TAM, and its active metabolites in plasma. This method offers a bioanalytical tool for assessing the pharmacokinetics of ABM and TAM. Therefore, this study makes a definite significant contribution to the field of bioanalytical research. Further validation in human plasma is required for future clinical or therapeutic drug monitoring applications, as the approach was developed in an animal model. Full article

Compound repurposing is an efficient method to save both time and costs by redirecting previously synthesized small molecules towards new biological targets. In this research, we employ computational methodologies to investigate and assess target engagement of small molecules as tyrosine kinase inhibitors (TKIs). Therefore, compounds TKI.2a, TKI.2b, TKI.6, TKI.16, TKI.19, and TKI.21b identified from our earlier research, undergo assessments of molecular similarity, docking studies, and pharmacophore modeling along with those discovered through database searches. Compounds TKI.2a, TKI.2b, TKI.6, and TKI.19 appear to exhibit multi-target tyrosine kinase inhibitory activities against VEGFR-2 (Vascular Endothelial Growth Factor Receptor), RET (proto-oncogene tyrosine–protein kinase receptor), PDGFRα (Platelet-Derived Growth Factor Receptor alpha), EGFR (Epidermal Growth Factor Receptor), and HER2 (Human Epidermal Receptor) receptors. Pharmacophore models were applied for ligand-based virtual screening using defined parameters to discover candidate compounds that exhibit drug-likeness with FDA (Food and Drug Administration)-approved tyrosine kinase inhibitors. Molecular docking studies identified lead compounds for each biological target based on their overall affinity values and established interactions. Compound ChEMBL2170947 was found to be the most promising candidate for the VEGFR-2 receptor, ChEMBL5019511 for PDGFRα, ChEMBL2216869 for EGFR, and ChEMBL3355044 for HER2. Full article

Background/Objectives: The prognostic significance of the uric acid-to-albumin ratio (UAR) in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has not been adequately investigated. This study aimed to investigate the association between baseline UAR and survival outcomes in this patient population. Methods: This retrospective study included HR-positive/HER2-negative metastatic breast cancer patients treated with ribociclib or palbociclib at Necmettin Erbakan University between May 2020 and April 2025. UAR was calculated by dividing the serum uric acid level (mg/dL) by the serum albumin level (g/dL). Based on receiver operating characteristic (ROC) analysis, the optimal cut-off value for UAR was identified as 1.0 (AUC = 0.67; sensitivity 68%; specificity 58%). Patients were subsequently classified into two groups as UAR < 1 and UAR ≥ 1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Independent prognostic factors were evaluated using Cox regression analyses. Results: A total of 118 eligible patients were included in the analysis, including 34 (28.8%) in the UAR < 1 group and 84 (71.2%) in the UAR ≥ 1 group. The proportion of postmenopausal patients was significantly higher in the UAR ≥ 1 group (p = 0.01). Kaplan–Meier analysis showed that median PFS was not reached in the UAR < 1 group, whereas it was 33.05 months in the UAR ≥ 1 group (log-rank p = 0.06). Median OS was not reached in the UAR < 1 group and was 50.7 months in the UAR ≥ 1 group (p = 0.017). Multivariate Cox regression analysis demonstrated that UAR < 1 was associated with improved PFS (HR = 0.65; 95% CI: 0.34–0.89; p = 0.04). Postmenopausal status emerged as an independent adverse prognostic factor for PFS (HR = 1.92; 95% CI: 1.10–4.05; p = 0.04). In addition, UAR < 1 was associated with a reduced risk of mortality in the OS analysis (HR = 0.61; 95% CI: 0.26–0.87; p = 0.01). Conclusions: Lower baseline UAR was associated with more favorable survival outcomes in HR-positive/HER2-negative metastatic breast cancer patients treated with CDK4/6 inhibitors. As an inexpensive and easily accessible biomarker derived from routine laboratory parameters, UAR may provide additional prognostic information for clinical risk stratification. Full article

Polydeoxyribonucleotide (PDRN) activates the adenosine A2A receptor (A2AR), triggering anti-inflammatory signaling and providing essential nucleotides for the salvage pathway, thereby helping bypass metabolic bottlenecks and promoting tissue repair. Combining PDRN with biochemical agents and physical stimuli represents a significant shift in medical treatment, moving from monotherapy to an integrated, multi-target regenerative approach. These combinatorial strategies effectively address the limitations of PDRN, such as its rapid degradation and diffusion, by simultaneously meeting the structural, metabolic, and signaling needs of injured tissues. The mechanism of action for PDRN involves a synergistic effect with hyaluronic acid, amplification of growth factors (e.g., Platelet-Rich Plasma (PRP), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF)), and enhancements from extracorporeal shockwave therapy (ESWT) and lasers. This results in a notable acceleration of the repair process for chronic wounds, musculoskeletal disorders, and neurological injuries. As intelligent delivery systems like responsive hydrogels and sustainable L-PDRN production continue to advance, these synergistic protocols are poised to redefine global standards of care in regenerative medicine and esthetic dermatology. Future clinical success will hinge on the standardization of sequence-specific protocols and large-scale validation to ensure long-term safety and efficacy. Full article

Background: Evaluation of gene-level copy number variants (CNVs) for diagnosis and therapeutic decision making has become standard of care with next-generation sequencing (NGS), immunohistochemistry (IHC), and/or fluorescence in situ hybridization (FISH) being used to detect gene amplifications/deletions in tumor tissue. In contrast to most solid tumors, CNS cancers are challenging to evaluate by resection and/or biopsy due to the associated risks with invasive brain surgery that can also result in death or associated morbidity and therefore alternate methods are required.Methods: This study presents the analytical validation of using quantitative PCR (qPCR) to detect gene CNVs directly from cerebrospinal fluid (CSF)-derived DNA and from the Ascent^TM low-pass whole genome sequencing (LP-WGS) libraries, demonstrating concordance with the gold standard of NGS/IHC/FISH used in tumor tissue. Results: The analytical sensitivity of qPCR to detect gene amplification calls for ERBB2 (erb-b2 receptor tyrosine kinase 2) was demonstrated to be 100% and that of EGFR (epidermal growth factor receptor) was 83%, with specificities of 96% and 100%, respectively. The analytical sensitivity of qPCR to detect gene deletions for CDKN2A/2B (cyclin-dependent kinase inhibitor 2A/2B) was 60% and that for MTAP (methylthioadenosine phosphorylase) was 100% with a specificity of 100% for all three genes. Ascent^TM was demonstrated to have a higher sensitivity (100%) when compared to qPCR for the same genes evaluated and demonstrated 100% positive agreement and 100% negative agreement with known CNV status. Conclusions: The results demonstrate that given the paucity of cells in CSF limiting the use of IHC and FISH, qPCR and Ascent^TM provide highly sensitive, novel, minimally invasive methods for the evaluation of gene copy number (CN) status to inform the diagnosis and management of CNS cancers. Full article

Cost-effective, fluorescence-based biodiagnostic devices have the potential to expand point-of-care (POC) testing in resource-limited settings, thereby creating new opportunities for accessible and decentralised diagnostics. The objective of this study is to investigate the performance of a newly designed and simplified system that uses several cost-effective sensors for use in a fluorescence-based biodiagnostic setup. A collecting setup that includes an elliptical mirror to focus emitted fluorescence onto the semiconductor sensors was designed for an intensity-based readout. The readout was realised by various photodiodes, photoresistors, phototransistors and one multi-pixel photon counter (MPPC). Over a range of fluorophore concentrations using serial dilutions of Rhodamine B (RhB), the limit of detection (LOD) and limit of quantification (LOQ) at system level were evaluated. With the exception of the photodiodes, the system demonstrated promising performance with all sensors. The system using the photoresistors achieved the lowest LOD but showed limited repeatability, while the system using the MPPC and phototransistors exhibited high repeatability. A proof-of-concept demonstrated the feasibility of a photoresistor-based configuration by using a sandwich immunoassay for the detection of the antigen Human Epidermal growth factor Receptor 2 (HER2) (100 nM). While this study has not yet encompassed the full spectrum of clinically relevant concentrations, it has yielded valuable insights to enable further enhancements, without the necessity for highly specialised or costly equipment. The limitations and necessary improvements for further developments are discussed. Full article

Background and Objectives: This study aimed to evaluate the association between systemic nicotine administration and histological and biochemical repair endpoints in an acetic acid-induced rat oral ulcer model. Materials and Methods: Thirty-six male Wistar rats were assigned to control, oral ulcer + saline, and oral ulcer + nicotine (1 mg/kg/day, s.c.) groups. Oral ulcers were induced with 70% acetic acid. After 15 days, buccal mucosa and plasma samples were collected for histopathological and biochemical analyses. Epithelial thickness and fibrosis were assessed histologically, while malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor-A (VEGF-A), and epidermal growth factor receptor (EGFR) were quantified. Results: Relative to controls, ulcer induction was associated with reduced epithelial thickness and increased fibrosis, MDA, and TNF-α levels. Compared with the oral ulcer + saline group, the nicotine-treated group showed greater epithelial thickness, lower fibrosis, lower MDA and TNF-α levels, and higher VEGF-A and EGFR levels at the study endpoint. No significant difference in VEGF-A was observed between the control and oral ulcer + saline groups. Conclusions: In this acetic acid-induced rat model, systemic nicotine administration was associated with improved endpoint histological and biochemical indices of oral ulcer repair. Because macroscopic wound closure, dose–response relationships, route comparisons, and direct mechanistic experiments were not included, these findings should be interpreted as preliminary preclinical associations rather than evidence of a direct causal effect of nicotine on wound healing. Full article

Background/Objectives: Triptolide (TP), a potent natural diterpenoid, exhibits anti-glioma activity, but faces significant clinical translation challenges, including poor water solubility, systemic toxicity such as hepatotoxicity, and inadequate tumor targeting. This study aimed to develop a novel epidermal growth factor receptor (EGFR)-targeted liposomal formula-tion, designated as TP-CTX-Lip (where CTX denotes cetuximab), to enhance the deliv-ery efficiency and therapeutic window of TP. Methods: The formulation was optimized using a uniform design approach (four factors, six levels) and prepared via thin-film hydra-tion–ultrasonication. The encapsulation of TP was supported by Fourier transform in-frared spectroscopy (FTIR) and thermal analysis (DSC/TGA), which revealed molecu-lar interactions (e.g., hydrogen bonding) with lipid components and a marked en-hancement in thermal stability, consistent with successful incorporation into the lipo-somal bilayer. The physicochemical properties, including the size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading, were characterized. In vitro release kinetics were evaluated in phosphate buffer (pH 7.4), and cytotoxicity was assessed in high-EGFR (U87-MG) and low-EGFR (SW1088) glioma cells. In vivo efficacy and developmental toxicity were investigated using zebrafish models. The op-timized TP-CTX-Lip demonstrated favorable characteristics: size = 131.3 ± 4.5 nm, PDI = 0.24 ± 0.006, zeta potential = −23.37 ± 0.27 mV, encapsulation efficiency = 85.83% ± 1.81%, and drug loading = 13%. In vitro release followed first-order kinetics dominated by Higuchi diffusion (79.0% ± 4% at 24 h). After 48 h of treatment, TP-CTX-Lip exhib-ited significantly enhanced cytotoxicity in U87-MG cells (IC50 = 10.4 ± 0.2 nM), com-pared with IC50 values of 42.8 nM in SW1088 cells and 45.3 nM for non-targeted lipo-somes. In the 3T3-L1 non-cancerous cell line, the 48 h IC50 value of TP-CTX-Lip (8.433 ± 0.954µM) was higher than that of the TP solution (2.173 ± 0.181µM) but lower than that of TP-Lip (25.78 ± 2.691µM). Specifically, in 3T3-L1 cells, the 48 h IC50 of TP-CTX-Lip (8.43 µM) was approximately 4-fold higher than that of free TP (2.17 µM), confirming its substantially reduced cytotoxicity against non-cancerous cells. Results: In comparison to TP-Lip and free FITC solution, the uptake rate of TP-CTX-Lip in U87-MG cells exhibited a significantly higher level. Specifically, the uptake rate for the TP-CTX-Lip group (57.46 ± 5.44%) was statistically significantly higher than that of TP-Lip (13.7 ± 2.33%) and the free FITC solution group (20.97 ± 1.60%) (p < 0.01). In zebrafish, TP-CTX-Lip reduced developmental toxicity, with LC50 increased 1.26 times to 5.733 μg/mL, and suppressed orthotopic U87-MG xenograft growth (p < 0.001), in-dicating an improved therapeutic window as reflected by the LC50/IC50 ratio. Conclusions: the EGFR-targeted TP-CTX-Lip significantly enhances the tumor selectivity and safety of TP, providing a promising strategy for targeted glioma therapy. Full article

The biologic and prognostic value of tumor human epidermal growth factor receptor 2 (HER2) expression in patients with advanced urothelial carcinoma (UC) who undergo systemic therapies remains controversial. A systematic search of English-language literature using PubMed, Scopus, and Cochrane Library was performed in October 2025 according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol to evaluate the prognostic value of tumor HER2 expression in predicting oncological outcomes of patients with advanced UC. The primary endpoints were recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Seventeen studies comprising 4909 patients were eligible. HER2 expression was significantly associated with inferior RFS (HR 1.68, 95% CI 1.16–2.42; p = 0.005) and CSS (HR 1.36, 95% CI 1.10–1.68; p = 0.004), but not with OS (HR 1.03, 95% CI 0.54–1.80) or PFS (HR 0.97, 95% CI 0.50–1.89), in patients with advanced UC. In conclusion, tumor HER2 expression may identify a subgroup of patients with advanced UC at increased risk of recurrence and cancer-specific mortality, supporting its potential role as a prognostic biomarker. However, standardized assessment and prospective studies are warranted to define its utility for risk stratification and therapeutic targeting. Full article

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality despite major advances in diagnostics and therapies. The prognosis remains poor, mostly due to late-stage presentation and molecular heterogeneity. Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. The development of EGFR tyrosine kinase inhibitors (TKIs) has significantly improved outcomes in patients with EGFR mutations. Variant allele frequency (VAF) is a quantitative genomic measure representing the proportion of sequencing reads harboring a given mutation. In NSCLC tissue, the EGFR mutation VAF reflects tumor clonality and intratumoral heterogeneity, and accumulating evidence suggests an association between EGFR VAF and response to EGFR-targeted TKIs. Methods: To address the limited synthesis of data on the relevance of EGFR mutation VAF in NSCLC, we conducted a narrative review of the literature using PubMed/MEDLINE and Embase databases and current clinical guidelines, synthesizing available evidence on EGFR VAF, including its biological, molecular, and therapeutic implications in EGFR-mutated disease. The review was structured in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) checklist. Results: EGFR VAF and on-treatment VAF dynamics are consistently associated with treatment response, progression-free survival, and overall survival in osimertinib-treated NSCLC. Baseline VAF enables risk stratification, early clearance kinetics predict durable benefit, and longitudinal VAF monitoring facilitates early detection of resistance. Importantly, the prognostic implications of VAF differ fundamentally between tissue-based and plasma-based measurements: high tissue VAF reflects clonal homogeneity and predicts favorable TKI response, whereas high plasma VAF indicates elevated tumor burden and is associated with inferior outcomes. In the second-line setting, the T790M/activating mutation ratio serves as a surrogate for resistance clonality and independently predicts osimertinib efficacy. Conclusions: EGFR VAF represents a promising dynamic molecular biomarker for treatment monitoring and precision decision-making in EGFR-mutated NSCLC. Full article

Advanced gastric (GAC) or gastroesophageal junction (GEJAC) adenocarcinoma continues to carry a poor prognosis. Understanding GAC/GEJAC at the molecular level has provided a new understanding and the basis for individualized approaches to treatment. The current biomarker-driven therapy focuses on four areas: microsatellite instability (MSI), human epidermal growth factor receptor-2 (HER2), programmed death ligand-1 (PD-L1) combined positive score, and claudin 18.2 (CLDN18.2). However, because of improving technology, the focus has shifted to cancer cell-surface proteins and peptides. Each of these GAC/GEJAC subgroups provides a different treatment pathway. The agents utilized to treat advanced GAC/GEJAC include immune checkpoint inhibitors (ICIs), chemotherapy, monoclonal antibodies (mAbs), and antibody–drug conjugate (ADC) therapy, as well as bispecific antibodies (BsAbs), but they are certainly not limited to the above. Drug development has shifted in recent years to establish different mechanisms that are attempting more sophisticated and targeted approaches, such as BsAbs and ADCs. Meanwhile, the development of cytotoxics has tapered off. Along with these developments in drug therapy, more therapies directed at CLDN18.2, HER2, MSI, EGFR, HER3 and trophoblast cell-surface antigen 2 (TROP2) are underway. Here we review future areas in advanced GAC, including zanidatamab’s potential role in HER2-positive advanced GAC and deciphering the abundance of anti-CLDN18.2, extending beyond investigative therapies. Full article

Background/Objectives: Genetic testing in Human Epidermal Growth Factor Receptor 2-negative (HER2−) metastatic breast cancer (mBC) is necessary to enable optimal treatment choices including poly(ADP-ribose)polymerase inhibitors (PARPis). The present study evaluated the implementation of genetic testing in a real-world setting to reveal and subsequently allow targeting of potential inadequacies and risk factors for low testing frequency. Methods: We performed a retrospective analysis including HER2− mBC patients treated at a single academic center starting from 10 April 2019 (date of European Medicines Agency (EMA) approval of Olaparib for germline breast cancer gene mutant (gBRCAm) HER2− mBC) to 7 September 2021. The primary objective of the study was to evaluate the rate of HER2− mBC patients that were recommended to undergo genetic testing by the multidisciplinary tumor board (MTB). The secondary objective was to identify factors that were associated with a higher likelihood of having undergone genetic testing. Results: In total, 47.6% (109 of 229) of HER2− mBC patients had been recommended to undergo genetic testing by the MTB. Of these informed patients, 89.0% (97 of 109) underwent genetic testing, of which 11.6% (11 of 95) had a germline BRCA mutation (gBRCAmut) and were eligible for PARPi treatment. In multivariate analysis, younger age (p-value: 0.0007), hormone receptor positive (HR+)/HER2− subtype (p-value < 0.0001) and positive family history for breast and ovarian cancer (p-value: 0.0001) were significantly associated with the performance of genetic counseling. Conclusions: The present study demonstrated low genetic counseling rates of HER2− mBC patients, especially in individuals without specific risk factors for hereditary breast cancer. Informed patients showed a high willingness to undergo genetic testing. Genetic testing revealed targetable mutations in over 10% of tested patients. Full article

Background: Neoadjuvant chemotherapy (NACT) response in breast cancer is primarily influenced by tumor biology; however, the independent role of host-related factors such as body mass index (BMI) remains unclear. This study evaluated clinicopathological predictors of a high Miller–Payne response after neoadjuvant chemotherapy in patients with stage II–III non-metastatic breast cancer, with particular focus on the role of body mass index. Methods: In this retrospective cohort study, 647 patients with stage II–III non-metastatic breast cancer treated with standard NACT between January 2010 and December 2020 at a single tertiary center were included. High pathological response was defined as Miller–Payne Grades 4–5. Clinical and tumor-related variables were analyzed, including age, menopausal status, body mass index, clinical stage, tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and Ki-67 proliferation index. Univariate and multivariable logistic regression analyses were performed to determine independent predictors of high pathological response. Results: A total of 647 patients were included (mean age: 49.18 ± 10.94 years; mean BMI: 28.45 ± 5.45 kg/m²), of whom 47.45% were postmenopausal. High Miller–Payne response (Grades 4–5) was observed in 40.96% of patients. High response was significantly associated with clinical stage (p = 0.034), tumor grade (p < 0.001), HER2 status (p < 0.001), ER status (p < 0.001), PR status (p < 0.001), and Ki-67 levels (p < 0.001). Median Ki-67 was higher in the high-response group (35.00% [IQR: 20.00–62.75] vs. 25.00% [IQR: 15.00–45.75], p < 0.001). No significant associations were observed for age (p = 0.299), BMI (p = 0.874), or menopausal status (p = 0.289). In multivariable analysis, HER2 positivity (adjusted OR = 3.71, 95% CI: 2.23–6.20, p < 0.001) and Ki-67 (adjusted OR = 1.01 per 1% increase, 95% CI: 1.00–1.02, p = 0.009) were independently associated with high response, whereas ER positivity (adjusted OR = 0.50, 95% CI: 0.25–0.98, p = 0.043) and postmenopausal status (adjusted OR = 0.37, 95% CI: 0.17–0.81, p = 0.013) were inversely associated. BMI was not independently associated with response (p = 0.964). Conclusions: Response to neoadjuvant chemotherapy appears to be mainly determined by tumor biology, particularly receptor status and proliferative activity, rather than anthropometric measures such as body mass index. Full article

Triple-negative breast cancer (TNBC) is one of the most aggressive and clinically challenging subtypes of breast cancer, defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. The lack of actionable molecular targets contributes to limited therapeutic options, frequent recurrence, and a high propensity for distant metastasis. Metastatic dissemination remains the principal cause of mortality in patients with TNBC and is driven by complex molecular mechanisms involving multiple interconnected signaling networks. This review summarizes current knowledge of the molecular mechanisms underlying metastatic progression in TNBC, with particular emphasis on signaling pathways that regulate tumor invasion, migration, and colonization of distant organs. We discuss the roles of key pathways, including PI3K/Akt, TGF-β, Wnt/β-catenin, NF-κB, and Rho/ROCK signaling, in the regulation of epithelial–mesenchymal transition, cytoskeletal remodeling, cancer stem cell phenotypes, and tumor–microenvironment interactions. A deeper understanding of these signaling networks may facilitate the identification of novel therapeutic targets and support the development of more effective strategies to limit metastatic disease in TNBC. Full article