Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110431 - 110431
Published: April 1, 2025
Language: Английский
Translational Lung Cancer Research, Journal Year: 2025, Volume and Issue: 14(2), P. 422 - 430
Published: Feb. 1, 2025
Immunotherapy (IO) exhibits poor therapeutic effect in epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). However, previous studies reveal different IO efficacy between exon 19 deletion (19 Del) and 21 L858R mutation (21 L858R). In this study, we aimed to evaluate the difference patients with EGFR Del L858R. data of response rate, disease control rate (DCR), progression-free survival (PFS), overall (OS) stratified by subtypes were extracted synthesized on random-effect model using odds ratios (ORs) for dichotomous hazard (HRs) 95% confidence interval (CI). Efficacy comparisons estimated through direct indirect methods respectively. A total 15 that involved 1,209 EGFR-mutant NSCLC treatment included Del, n=676; L858R, n=533). Based from 11 meta-analysis, had shorter PFS (HR =1.55; CI: 1.21-1.98; P=0.001) OS =1.36; 1.04-1.78; P=0.02) poorer DCR (OR =0.51; 0.29-0.87; than those significantly. Indirect meta-analysis four trials showed same result significantly =1.50; 1.09-2.07; P=0.01) Subgroup analyses also similar tendency more clinical benefit compared no matter whether monotherapy or combination. For patients, superior Del.
Language: Английский
Citations
1
Archiv der Pharmazie, Journal Year: 2025, Volume and Issue: 358(4)
Published: April 1, 2025
ABSTRACT The epidermal growth factor receptor (EGFR) family, comprising tyrosine kinases (RTK) such as EGFR and HER2, plays a critical role in various signaling pathways related to cell proliferation, differentiation, growth. overactivation due aberrant can lead cancers, including non‐small lung cancer (NSCLC). To develop treatment for EGFR‐related NSCLC, several kinase inhibitors (TKIs) were designed: gefitinib, erlotinib, first‐generation; neratinib, dacomitinib second‐generation; osimertinib, lazertinib third‐generation, examples. However, the acquired resistance by mutations T790M C797S together with exon 20 insertion mutations, these drugs do not provide promising results NSCLC patients. development of fourth‐generation like EAI045 further innovative overcome this problem is must cure NSCLC. Among these, pyrazoline‐thiazole scaffolds are found effective EGFR‐HER2 against making them drug candidates. Although structures obtained so far family meaningful insights into mechanisms, quality quantity insufficient elucidate complete functions This review evaluates investigates their relation
Language: Английский
Citations
0
Journal of Contemporary Medical Practice, Journal Year: 2025, Volume and Issue: 7(1), P. 123 - 128
Published: Jan. 31, 2025
Objective: To analyze the correlation between Biological Effects of EGFR Exon 19 and 21 Mutations Clinical Imaging characteristics in Lung Adenocarcinoma. Methods: The clinical imaging data patients with lung adenocarcinoma who had undergone genetic testing Baotou Cancer Hospital from July 2021 to May 2024 were retrospectively collected, chest CT examination was performed before treatment evaluate mutant wild type subtype (exon 21) features, compared groups. Univariate analysis used differences statistically significant indicators into binary logistic regression screen out independent predictors. Results: Compared wild-type EGFR19 mutations, females, small lesions maximum diameter, spiculation, pleural indentation, low INCTR more common mutation group, males, larger no higher (all p <0.5). stic showed that diameter (OR=90.825, 95%CI 2.023-4078.299, P=0.020) (OR=0.692, 95%C 0.516-0.927, P=0.014) a risk factor for mutation. In comparison EGFR21 wild-type, female, non-smoking patients, vessel convergeence sign, sign (OR=18.582, 1.848-186.870, P=0.013) (OR=0.793, 0.687-0.915, P=0.002) factors
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1483 - 1483
Published: Feb. 11, 2025
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated remarkable efficacy in treating non-small cell lung cancer (NSCLC), but acquired resistance greatly reduces and poses a significant challenge to patients. While numerous studies investigated the mechanisms underlying EGFR-TKI resistance, its complexity diversity make existing understanding still incomplete. Traditional approaches frequently struggle adequately reveal process of drug development through mean value analysis at overall cellular level. In recent years, rapid single-cell RNA sequencing technology has introduced transformative method for analyzing gene expression changes within tumor cells resolution. It not only deepens our microenvironment heterogeneity associated with also identifies potential biomarkers resistance. this review, we highlight critical role research, particular focus on application exploring EGFR-TKI-acquired NSCLC. We emphasize elucidating mechanism promise informing more precise personalized treatment strategies. Ultimately, approach aims advance NSCLC toward new era precision medicine.
Language: Английский
Citations
0
Targets, Journal Year: 2025, Volume and Issue: 3(1), P. 7 - 7
Published: Feb. 20, 2025
Bombesin receptor subtype-3 (BRS-3) is a type 1 G-protein-coupled (GPCR). BRS-3 an orphan GPCR that structurally related to neuromedin B and gastrin-releasing peptide receptors. When activated, causes phosphatidylinositol turnover in lung cancer cells. stimulates tyrosine the phosphorylation of epidermal growth-factor (ErbB1); however, it unknown whether transactivates ErbB2/HER2. Adding nonpeptide allosteric agonist MK-5046 or BA1 cell line NCI-H727 BRS-3-transfected NCI-H1299 cells increased HER2/ERK2. This increase was antagonized by antagonist Bantag-1 small-molecule ML-18. The HER2/ERK caused inhibited ROS inhibitors N-acetylcysteine Tiron (superoxide scavengers). reactive oxygen species, which NAC Tiron. non-small (NSCLC) colony formation, whereas Bantag-1/ML-18 proliferation. These results indicate cells, activation regulates HER2 transactivation ROS-dependent manner, can mediate tumor growth. raise possibility use HER2-inhibiting compounds alone combination with other agents could represent novel approach treatment these tumors.
Language: Английский
Citations
0
The Journal of Gene Medicine, Journal Year: 2025, Volume and Issue: 27(3)
Published: March 1, 2025
ABSTRACT Background The expression and functional role of pyrroline‐5‐carboxylate reductase 1 (PYCR1) in esophageal squamous cell carcinoma (ESCC) remain poorly understood. This study aimed to elucidate the underlying mechanisms PYCR1 ESCC. Methods We utilized an ESCC tissue microarray coupled with immunohistochemical staining assess variability protein among patients evaluate its clinical relevance. was silenced lines short hairpin RNA (shRNA), followed by assays (colony formation, caspase 3/7 activity, methylthiazol tetrazolium, wound healing, migration/invasion assays) progression. In vivo, mouse tumor xenograft models were used examine PYCR1's impact on growth. To identify downstream targets pathways, we conducted coimmunoprecipitation, mass spectrometry, immunofluorescence, proteomic analyses, validated western blotting rescue experiments. Results Our findings demonstrated a consistent upregulation tissues. Both vitro vivo studies revealed that suppression significantly inhibited progression, impacting key processes such as proliferation, apoptosis, migration, invasion. Mechanistically, shown interact EGFR, promoting progression metastasis activating PI3K/AKT/mTOR signaling which are integral aggressive behavior disease. Rescue experiments further confirmed EGFR overexpression effectively reversed inhibitory effects knockdown cells. Conclusion highlights critical driving metastasis, underscoring potential promising therapeutic target for managing this malignancy.
Language: Английский
Citations
0
BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)
Published: April 8, 2025
Language: Английский
Citations
0
Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)
Published: April 13, 2025
The prognosis of ground glass opacity featured lung adenocarcinomas (GGO-LUAD) is significantly better than that solid nodule (SN-LUAD), but the underlying reasons remain unclear. Ki-67 and cell cycle regulator proteins are highly expressed in many cancers linked to prognosis. This study aims investigate their differential expression LUAD with different radiological subtypes. Patients resected pathological stage 0-III our department between July 2019 March 2022 were retrospectively reviewed. All included patients divided into four groups based on consolidation-to-tumour ratio (CTR), we focuses evaluating regulatory (CCNA2, CCNB1, CCND1, P16, P21, TOP2A, TP53, pRb) CTR. A total 481 included, 108 pure (PGGO, CTR = 0) group, 103 GGO-dominant (GGO-D, 0 < ≤ 0.5) 74 SN-dominant (SN-D, 0.5 1) 196 (SN, group. was higher elderly (P 0.05), former or current smokers 0.0001), males poorly differentiated tumors spread through air spaces (STAS) advanced 0.0001). Regardless age, gender, smoking status epidermal growth factor receptor (EGFR) mutation status, GGO-LUAD demonstrated lower compared SN-LUAD. (except P21) PGGO, GGO-D, SN-D SN However, there no significant difference among groups. SN-LUAD, which may explain behind excellent GGO-LUAD.
Language: Английский
Citations
0
ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown
Published: April 16, 2025
Lung cancer remains one of the most lethal cancers globally, with nonsmall cell lung (NSCLC) representing predominant subtype. Despite significant advancements in targeted therapies, overcoming therapeutic resistance NSCLC a challenge, particularly cases resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Here, we developed target-specific, protein nanoparticles using Aquifex aeolicus lumazine synthase (AaLS), which were engineered simultaneously display multiple TRAIL molecules EGFR-binding ligands, including EGFR affibody (Afb) or anti-EGFR nanobodies (7D12, 9G8, EgB4). These utilize enhance selective targeting EGFR-overexpressing adenocarcinoma (PC9, HCC827, A549) squamous carcinoma (H226) cells, regardless mutations within intracellular domain EGFR, are primarily driven by tyrosine commonly used as first-line treatments therapy. The codisplayed ligands attachment TRAIL-displaying cells stabilizing interactions promoting surface clustering improving engagement death receptors (DRs). This sustained interaction significantly amplifies TRAIL-mediated apoptotic signaling, effectively both EGFR-TKI cells. Our findings suggest that dual ligand-displaying DRs represent promising strategy potentiate efficacy circumvent NSCLC.
Language: Английский
Citations
0
Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110431 - 110431
Published: April 1, 2025
Language: Английский
Citations
0