Search Results (567)

Background: Non-small cell lung carcinoma (NSCLC) is the most prevalent form of lung cancer, and its progression is closely associated with constitutive activation of signal transducer and activator of transcription 3 (STAT3). This study used surface plasmon resonance (SPR) technology to develop a STAT3-targeting recognition system and identify natural STAT3-targeting compounds from the traditional Chinese medicine Psoralea corylifolia and to evaluate their anti-NSCLC activities, with particular attention to reactive oxygen species (ROS) regulation. Methods: The SPR biosensor immobilized with STAT3 was used to screen and enrich STAT3-binding constituents of Psoralea corylifolia, and to determine ligand-STAT3 affinities. Molecular docking was performed to characterize interactions within the STAT3 SH2 domain. Functional effects were assessed in A549 cells using proliferation and scratch migration assays. Antioxidant capacity was evaluated via hydroxyl radical and superoxide anion scavenging assays, and intracellular ROS levels were measured in hydrogen peroxide (H₂O₂)-induced oxidative stress models in human umbilical vein endothelial cells (HUVECs) and A549 cells. Results: SPR analysis showed that psoralen and isopsoralen bind to STAT3, with equilibrium dissociation constants (KD) of 80.92 µM and 28.11 µM, respectively. Molecular docking further confirmed their interaction with the STAT3 SH2 domain. Both compounds inhibited A549 proliferation and reduced migration. Beyond direct STAT3 inhibition, both compounds demonstrated notable free radical scavenging activity. In a H₂O₂-induced oxidative stress model, pretreatment with psoralen or isopsoralen significantly reduced ROS levels in HUVECs, while increasing ROS accumulation in A549 lung cancer cells. Conclusions: This work identifies psoralen and isopsoralen as novel dual-function STAT3 inhibitors that exert anti-NSCLC effects through combined STAT3 suppression and context-dependent ROS modulation, and demonstrates the utility of SPR for screening bioactive natural products. Full article

Background: Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17–20% of the human genome. These retroelements are normally silenced early in embryonic development through epigenetic mechanisms and reawakened during oncogenesis, leading to transcriptional dysregulation, genomic instability, and immune evasion. Methods: In the present study, we categorized LINE-1 transcripts across 121 non-small cell lung cancer (NSCLC) cell lines from the Cancer Cell Line Encyclopedia (CCLE) by subfamily, length, orientation, chromosomal origin, and distribution. In addition, high-prevalence insertions were mapped to nearby genes to assess potential functional interactions. Results: LINE-1 transcript abundance and length in NSCLC were dominated by evolutionarily young subfamilies, particularly L1HS and L1PA2 through L1PA5. Chromosomal patterns were conserved across NSCLC subtypes, with modest enrichment of L1HS activity on Chromosome 4 and the X Chromosome. The lung squamous cell carcinoma (LSQCC) subtype exhibited the highest total levels of L1HS expression relative to other NSCLC subtypes. Race modestly influenced LINE-1 transcript abundance, with cell lines derived from self-identified African American individuals showing elevated overall LINE-1 and L1HS expression. Age showed a weak positive correlation with total LINE-1 abundance. Integrative analysis revealed recurrent hotspots at 22q12.1 and 20p11.21 that were transcriptionally active across subtypes and coincided with previously reported intact LINE-1 elements active in epithelial cancers. Recurrent insertions were located near cancer-associated genes, including RB1, NEDD4, FTO, LAMA2, NOD1, and KCNB2, implicating LINE-1 activity in cis-regulatory remodeling of oncogenic pathways. Conclusions: Together, these findings indicate that LINE-1 transcript heterogeneity in NSCLC is shaped by host genomic architecture and conserved functional hotspots, providing new insights into the mechanisms of genetic and epigenetic dysregulation associated with LINE-1 retroelements. Full article

Background/Objectives: The development of small-molecule agents that selectively target DNA replication remains a central strategy in anticancer drug discovery. In this study, we report the biological characterization of a novel 6-nitro-benzodioxin-naphthalimide (NI) derivative (compound 5a), evaluated as a potential DNA-targeted anticancer lead. Methods/Results: The antiproliferative activity of 5a was assessed in a small panel of human lung carcinoma cell models (A549, H1299) and a non-malignant control (MRC-5), revealing pronounced cytotoxic effects in tumor cells, accompanied by favorable selectivity indices. Mechanistic investigations demonstrated that treatment with 5a results in strong inhibition of DNA synthesis, as evidenced by a marked reduction in EdU incorporation and a robust induction of the DNA damage marker γH2AX. These effects were associated with cell-cycle perturbations characterized by accumulation in G₁ and G₂/M phases, followed by activation of apoptotic pathways. Importantly, clonogenic survival assays confirmed that even transient exposure to 5a leads to a sustained loss of proliferative capacity, indicating irreversible long-term cellular damage. These results support a replication stress-driven mechanism of action for compound 5a, consistent with interference in DNA-associated processes during S phase. Conclusions: While the precise molecular initiating event remains to be elucidated, the observed biological profile positions 5a as a promising DNA-targeted lead structure with potential for further pharmaceutical optimization. These findings provide a solid foundation for the continued development of naphthalimide-based compounds as anticancer agents within a pharmaceutically relevant framework. Full article

Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy. Full article

This study reports the exclusive and rapid synthesis of twenty-four derivatives of 1-((mono/bis)trifluoromethyl)phenyl-3-(4-arylthiazol-2-yl)thioureas (series 7, 9 and 11), along with their antimicrobial activities against Candida albicans, Mycobacterium smegmatis and seven additional bacterial strains. The anticancer potential of these compounds was evaluated against various human cancer cell lines, including A549 (lung adenocarcinoma), HeLa (cervical carcinoma), IMR32 (neuroblastoma), MCF-7 (breast adenocarcinoma), HCT116 (colon cancer) and DU145 (prostate cancer). Among these, 1-(3,5-bistrifluoromethylphenyl)-3-(thiazol-2-yl)thiourea (7i) and 1-(4-trifluoromethylphenyl)-3-(4-(3-chlorophenyl)thiazol-2-yl)thiourea (11h) demonstrated significant antimicrobial activity against M. luteus, S. aureus, S. aureus 1 and C. albicans. Additionally, 1-(4-(3-chlorophenyl)thiazol-2-yl)-3-(3-trifluoromethylphenyl)thiourea (9g) and 1-(4-trifluoromethylphenyl)-3-(4-(2-fluorophenyl)thiazol-2-yl)thiourea (11g) showed activity against Mycobacterium smegmatis. The bioassay tests indicated that many of the thiourea derivatives exhibited moderate activity against the A549, HeLa, MCF-7 and HCT116 cancer cell lines. Full article

Requirements for novel effective antiviral agents against SARS-CoV-2 emphasizes the importance of robust in vitro screening platforms. We developed a test system based on spike-pseudotyped lentiviruses, carrying either luc+ or EGFP reporter genes as a payload, and a human non-small cell lung carcinoma (NSCLC) cell line, overexpressing ACE2 (H1299-hACE2). The cell origin makes our system resemble lung epithelium infection. Transmission electron microscopy confirmed that the spike glycoproteins on the pseudotyped lentiviral particles resemble native SARS-CoV-2 spike glycoproteins, thus validating their use in inhibitor screening. H1299-hACE2 cells showed significantly higher infection rate (p < 0.005) with spike-pseudotyped lentiviruses compared to parental H1299 cells, as determined by luciferase and fluorescence assays. The susceptibility of the stable H1299-hACE2 cell line to a broad panel of SARS-CoV-2 variants (Wuhan, Beta, Delta, Omicron) was assessed here for the first time in a unified experimental setting. Infection of H1299-hACE2 cells with SARS-CoV-2 induced cell fusion and syncytium formation with subsequent cell death. The developed pseudovirus-based assay was further used for assessment of the antiviral properties of derivatives of 1,7,7-trimethyl-[2.2.1]-bicycloheptane-potential spike protein inhibitors, which possess moderate activity against lentiviral particles. The H1299-hACE2/spike-pseudotyped lentivirus assay is, therefore, a reliable, high-efficiency platform for screening spike-mediated entry inhibitors. The cell line obtained during the development of the platform can be used to isolate and study new variants of SARS-CoV-2. Full article

Background: Advances in molecular pathology have transformed NSCLC (Non-Small Cell Lung Cancer) diagnosis, prognosis, and treatment by enabling precise tumor characterization and targeted therapeutic strategies. We review key genomic alterations in NSCLC, including EGFR (epidermal growth factor receptor) mutations, ALK (anaplastic lymphoma kinase) and ROS1 (ROS proto-oncogene 1) rearrangements, BRAF (B-Raf proto-oncogene serine/threonine kinase) mutations, MET (mesenchymal–epithelial transition factor) alterations, KRAS (Kirsten rat sarcoma) mutations, HER2 (human epidermal growth factor receptor 2) alterations and emerging NTRK (neurotrophic receptor tyrosine kinase) fusions and AXL-related pathways. Methods: A total of 48 patients with NSCLC was analyzed, including 22 women and 26 men (mean age 70 years, range 44–86). Tumor specimens were classified histologically as adenocarcinomas (n = 81%) or squamous cell carcinomas (n = 19%). Smoking history, PD-L1 (programmed death-ligand 1) expression, and genetic alterations were assessed. NGS (Next-generation sequencing) identified genomic variants, which were classified according to ACMG (American College of Medical Genetics and Genomics) guidelines. Results: The cohort consisted of 29 former smokers, 13 current smokers, and 5 non-smokers (12%), with a mean smoking burden of 33 pack years. PD-L1 TPS (tumor proportion score) was ≥50% in 10 patients, ≥1–<50% in 22, and <1% in 15 patients. In total, 120 genomic variants were detected (allele frequency ≥ 5%). Of these, 52 (43%) were classified as likely pathogenic or pathogenic, 48 (40%) as variants of unknown significance, and 20 (17%) as benign or likely benign. The most frequently altered genes were TP53 (tumor protein p53) (31%), KRAS and EGFR (15% each), and STK11 (serine/threonine kinase 11) (12%). Adenocarcinomas accounted for 89% of all alterations, with TP53 (21%) and KRAS (15%) being most common, while squamous cell carcinomas predominantly harbored TP53 (38%) and MET (15%) mutations. In patients with PD-L1 TPS ≥ 50%, KRAS mutations were enriched (50%), particularly KRAS G12C and G12D, with frequent co-occurrence of TP53 mutations (20%). No pathogenic EGFR mutations were detected in this subgroup. Conclusions: Comprehensive genomic profiling in NSCLC revealed a high prevalence of clinically relevant mutations, with TP53, KRAS and EGFR as the dominant drivers. The strong association of KRAS mutations with high PD-L1 expression, irrespective of smoking history, highlights the interplay between genetic and immunological pathways in NSCLC. These findings support the routine implementation of broad molecular testing to guide precision oncology approaches in both adenocarcinoma and squamous cell carcinoma patients. Full article

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care. Full article

Background: Conventional absorption-based computed tomography has a limited ability to resolve lung microarchitectures that are critical for histological subtype discrimination. This study evaluated the potential of X-ray Dark-Field Imaging Computed Tomography (XDFI CT) using synchrotron radiation for non-destructive, three-dimensional visualization of human lung cancer microstructures. Methods: Surgically resected human lung cancer specimens (n = 4) were examined, including acinar-predominant adenocarcinoma (n = 1), adenocarcinoma after concurrent chemoradiation therapy (n = 1), keratinizing squamous cell carcinoma (n = 1), and metastatic hepatocellular carcinoma in the lung (n = 1). Image acquisition was performed at beamline BL-14B of the Photon Factory (Tsukuba, Japan), using a monochromatic 19.8 keV synchrotron X-ray beam and a crystal analyzer-based refraction-contrast optical system. Imaging findings were qualitatively correlated with corresponding histopathological sections. Results: Synchrotron radiation XDFI CT enabled clear visualization of normal distal lung microanatomy, including alveolar walls and associated vascular structures, which served as internal references adjacent to tumor regions. Distinct microstructural features—such as invasive growth patterns, fibrotic or keratinized stroma, necrosis, and treatment-related remodeling—were identifiable and varied according to histological subtype. Tumor–normal tissue transitional zones were consistently delineated in all specimens. Conclusions: Synchrotron radiation XDFI CT provides high-resolution, non-destructive volumetric imaging of lung cancer tissues and reveals subtype-associated microarchitectural features. This technique may complement conventional histopathology by enabling three-dimensional virtual histologic assessment of lung cancer specimens. Full article

Background: Breast cancer is the most prevalent cancer in women, and metastatic breast cancer remains a major cause of cancer-related deaths. Resveratrol (RSV) is a natural compound found in various plants and is known to exhibit various anti-cancer effects. The present study aims to investigate the therapeutic effects and mechanisms of RSV in inhibiting breast cancer metastasis in a murine model of 4T1 breast tumor that shares close molecular features with human triple negative breast cancer. Methods: Murine breast cancer 4T1 cells were used to examine the effects of RSV on breast cancer metastasis and epithelial–mesenchymal transition (EMT). In vitro cell proliferation and Transwell migration assays and in vivo 4T1 tumor transplantation models were established in female Balb/c mice to determine the anti-metastatic effects of RSV and its mechanism of action. Results: RSV significantly inhibited 4T1 tumor cell migration and significantly decreased expression levels of EMT markers Snail and Vimentin, as well as the nuclear translocation of β-catenin both in vitro and in vivo. Knockdown of β-catenin similarly reduced the expression levels of EMT markers. RSV significantly decreased the number of lung metastases in 4T1-implanted mice by inhibiting Wnt/β-catenin signaling pathway activation. RSV (150 mg/kg/day) reduced the number of visible tumor metastatic nodules and the histological count of metastatic lung carcinomas by 51.82% and 62.58%, respectively, compared to vehicle administration. Conclusions: Our study provides important new mechanistic insight into the strong anti-cancer effects of RSV in inhibiting 4T1 breast cancer metastasis by preventing Wnt/β-catenin signaling pathway-mediated epithelial–mesenchymal transition. These findings suggest the therapeutic potential of RSV as a promising drug in the treatment of metastatic breast cancer. Full article

Background: Cancer epidemiology data for people living with human immunodeficiency virus (PLWH) in Thailand, particularly in the era of combination antiretroviral therapy (ART), remain limited. In this study, we describe the prevalence, temporal trends, clinical characteristics, and survival outcomes of patients with AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs). Methods: We retrospectively reviewed adult PLWH diagnosed with malignancy at Songklanagarind Hospital in Thailand during 2003–2023. Demographic, human immunodeficiency virus (HIV)-related, and clinical data were analyzed using chi-square and Wilcoxon rank-sum tests and the Kaplan–Meier method. Results: Among 444 patients, 231 had NADCs and 213 had ADCs. The NADC proportion increased markedly over time. Common ADCs included non-Hodgkin lymphoma and cervical cancer; common NADCs included lung cancer, non-nasopharyngeal head and neck cancer, and hepatocellular carcinoma. Compared with patients with ADCs, those with NADCs were older, more often male, and had higher proportions of undetectable HIV viral load, CD4 counts ≥200 cells/µL, and ART use. Approximately one-third of patients presented with advanced-stage disease, and the median overall survival was 15.9 months. Conclusions: Over two decades, NADCs have become the predominant malignancy in Thai PLWH, associated with older age, male sex, and improved immune function. This reflects the evolving cancer risk in the era of combination ART. We suggest employing multidisciplinary approaches involving HIV and cancer care to improve survival outcomes and integrating age-appropriate screening for common NADCs into HIV care. Full article

Objectives: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by rapid proliferation, early metastasis, and limited therapeutic response. Metabolic reprogramming is increasingly recognized as a key feature of small cell lung cancer progression, yet the contribution of specific metabolic enzymes remains incompletely understood. This study aimed to investigate the role of asparagine synthetase in small cell lung cancer tumorigenicity and disease progression. Methods: Integrative analyses were performed using public transcriptomic datasets, proteomic profiling, and functional assays in vitro and in vivo. Asparagine synthetase expression levels were evaluated in normal lung, non-small cell lung cancer, and small cell lung cancer tissues using public microarray datasets. Loss of function studies were conducted using shRNA mediated knockdown in murine and human small cell lung cancer cell models. Tumor growth and survival were assessed using xenograft mouse models. Results: Asparagine synthetase expression was significantly elevated in small cell lung cancer compared with normal lung and non-small cell lung cancer tissues. Genetic depletion of asparagine synthetase impaired cellular proliferation and colony forming capacity in vitro. In vivo, asparagine synthetase knockdown suppressed tumor growth and was associated with prolonged survival in xenograft mouse models. Conclusions: These findings demonstrate that asparagine synthetase contributes to tumor growth and metabolic adaptability in small cell lung cancer. The results support a functional role for asparagine synthetase in malignant progression and suggest that targeting asparagine metabolism may represent a potential therapeutic approach in aggressive small cell lung cancer. Full article

The development of antibiotic resistance has become a global health challenge, resulting in approximately 800,000 deaths per year. The rapid rise in multidrug-resistant (MDR) pathogens has prompted an urgent need for antimicrobial alternatives. Punica granatum L. peel has long been valued for its rich bioactive polyphenols with potent antimicrobial properties. In this study, P. granatum L. peel extract (PGPE) was integrated with chitosan nanoparticles (CH-PGPE) to enhance antimicrobial efficacy while minimizing potential cytotoxicity. The antimicrobial potential of PGPE and CH-PGPE was evaluated with agar well diffusion, disk diffusion, and minimum inhibitory concentration (MIC) analyses against standard ATCC and clinical MDR strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. MTT assay evaluated the biocompatibility and anti-proliferative potential of PGPE on ARPE-19 (normal retinal pigment epithelial), HeLa (human cervical cancer), and A549 (human lung carcinoma) cell lines. PGPE exhibited antibacterial activity, and CH-PGPE reduced MIC values by approximately two-fold. Both PGPE and CH-PGPE demonstrated comparable or superior inhibition compared to several conventional antibiotics, particularly against MDR strains. The MTT assay revealed that PGPE was non-cytotoxic to normal ARPE-19 cells, while exhibiting the highest antiproliferative potency against A549 cells and a moderate inhibitory response in HeLa cells. The nanoparticle-supported formulation enhanced the antimicrobial efficacy of PGPE and also exhibited selective anti-proliferative activity against cancer cells without affecting normal cells. Full article

Carotol, the major sesquiterpene alcohol in carrot essential oil, possesses notable cytotoxic activity against various cancer cell lines, yet its metabolic fate remains poorly understood. This study explored microbial biotransformation as a tool for generating novel carotol derivatives with potential pharmacological value. Seventeen microbial strains were screened, with Absidia coerulea ATCC 6647 identified as the most effective biocatalyst. Preparative-scale fermentation with this strain afforded three new metabolites, CM1, CM2, and CM3, in yields of 30%, 9.96%, and 3.28%, respectively, which were structurally characterized by 1D and 2D NMR, HRMS, and single-crystal X-ray diffraction. These were identified as 9α-hydroxydaucol (CM1), 9α,13-dihydroxydaucol (CM2), and a diol derivative of daucol (CM3). Cytotoxicity evaluation against human carcinoma cell lines (HepG-2, HCT-116, MCF-7, A-549) and normal lung fibroblasts (MRC-5) revealed that carotol exhibited notable activity with IC₅₀ values of 25.68 and 28.65 µM against HCT-116 and A-549 cell lines, respectively. Among the metabolites, CM2 showed selective cytotoxicity with IC₅₀ values of 180.64 (HCT-116) and 138.21 µM (A-549), indicating that microbial transformation modulates the cytotoxic profile of carotol and yields metabolites with distinct bioactivity patterns. Molecular docking studies further revealed that carotol and CM2 demonstrated higher binding affinities and more stable interactions with human NADPH oxidase, suggesting that inhibition of this enzyme may underlie their cytotoxic effects. This work provides the first detailed microbial biotransformation pathway of carotol, highlighting A. coerulea as a promising source of new hydroxylated metabolites. The results underscore the potential of carotol derivatives in anticancer drug development and warrant further pharmacokinetic studies. Full article

Lung squamous cell carcinoma (LUSC) is the second most prevalent type of lung cancer worldwide. Despite its global health burden, the molecular mechanisms driving LUSC remain poorly characterized, posing considerable challenges for the development of targeted preventive therapies. Here, by integrating human plasma proteomes (n = 54,219) with GWAS summary data for LUSC (7426 cases and 55,627 controls), we performed genome-wide Mendelian randomization (MR) and colocalization analyses to identify potential druggable targets associated with LUSC risk. After applying Bonferroni correction, sensitivity analyses, and reverse causation detection, we identified 12 potential druggable proteins significantly associated with LUSC risk. Five of these proteins (DOK2, FKBPL, NCF2, PDIA3, and TCL1A) showed strong evidence of colocalization. Furthermore, protein–protein interaction (PPI) networks and druggability assessments were used to refine therapeutic target selection. Additionally, mediation analyses were performed to elucidate the mediating effects of modifiable risk factors on the relationship between plasma proteins and LUSC risk, and we identified 14 modifiable risk factors that could mitigate LUSC risk through targeted interventions. More importantly, we stratified the 12 proteins into four tiers based on colocalization, differential expression, PPI networks, and druggability potential. Notably, DOK2 emerged as a Tier 1 target, while FKBPL, NCF2, AXL, and PDIA3 were classified as Tier 2 targets, representing promising candidates for further drug development. Overall, we identified 12 proteins with druggable potential associated with LUSC risk and demonstrated how modifiable risk factors mediate these associations. These findings advance our understanding of LUSC etiology and provide a foundation for developing targeted therapeutic strategies while emphasizing the importance of addressing modifiable risk factors in both prevention and treatment efforts. Full article