The role of PD-L1 in EGFR-mutant non-small cell lung cancer

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 12, 2025

Lung cancer remains the leading cause of cancer-related deaths globally. In China, nearly half non-small cell lung (NSCLC) patients carry epidermal growth factor receptor (EGFR) mutations. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved prognosis for with mutations and are considered preferred treatment these individuals. Programmed death-ligand 1 (PD-L1) expression levels now widely used as a biomarker to predict effectiveness PD-1/PD-L1 immunotherapy in NSCLC. Additionally, impact PD-L1 on efficacy EGFR-TKIs has garnered considerable attention from researchers. This review explores recent studies epidemiology clinical outcomes associated NSCLC harboring driver gene

Language: Английский

---

MYC Overexpression Enhances Sensitivity to MEK Inhibition in Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 588 - 588

Published: Jan. 12, 2025

MEK inhibitors, such as trametinib, have shown therapeutic potential in head and neck squamous cell carcinoma (HNSCC). However, the factors influencing cancer sensitivity resistance to inhibition remain poorly understood. In our study, we observed that significantly reduced expression of MYC, a transcription factor critical for response. MYC overexpression markedly enhanced HNSCC cells evidenced by delayed wound healing colony formation. Cell cycle analysis revealed trametinib induced G1 phase arrest, whereas accelerated progression, with induction p27 p21 diminished decreases E2F1 phospho-Ser2/5 levels. Flow cytometry protein analyses demonstrated amplified trametinib-induced apoptosis DNA damage, elevated levels pro-apoptotic markers (p53, cleaved PARP, BIM) γH2AX. vivo xenograft models confirmed these findings, showing increased MYC-overexpressing tumors. Moreover, autophagy cells, resistance. Inhibiting further apoptotic death. These findings suggest play crucial roles HNSCC’s response inhibition. Combining may improve outcomes HNSCC.

Language: Английский

---

Long-term chronic exposure to benzo[a]pyrene and catechol induced multidrug resistance in lung cancer cells

Environmental Pollution, Journal Year: 2025, Volume and Issue: 369, P. 125859 - 125859

Published: Feb. 14, 2025

Language: Английский

---

Expression and clinical significance of programmed cell death protein 1/programmed death-ligand 1 in non-small cell lung cancer patients with rare mutations of epidermal growth factor receptor gene: A retrospective cohort study

CytoJournal, Journal Year: 2025, Volume and Issue: 22, P. 36 - 36

Published: April 1, 2025

Objective Lung cancer represents a major global health issue and serves as leading cause of cancer-related deaths, with non-small cell lung (NSCLC) accounting for considerable proportion these cases. This study aimed to investigate the expressions clinical importance programmed death protein 1 (PD-1) death-ligand (PD-L1) in patients rare mutations epidermal growth factor receptor ( EGFR ) gene NSCLC. Material Methods A retrospective analysis including 121 NSCLC was performed. Immunohistochemistry conducted assess PD-L1 expression, were categorized into PD-L1-negative (PLN, n = 95) PD-L1-positive (PLP, 26) groups. PD-1 expression also evaluated, divided PD-1-negative (PN, 93) PD-1-positive (PP, 25) The associations among PD-L1/PD-1 demographic characteristics, progression-free survival (PFS), overall (OS), 5-year period analyzed. Results Significant negative correlations observed between PFS (r −0.202, R 2 0.041, P 0.026) OS −0.204, 0.042, 0.024). PLN group exhibited significantly longer (13.47 ± 3.58 months) than PLP (11.67 3.67 months; t 2.222, 0.032) (21.39 5.69 compared (18.65 4.32 2.664, 0.010). For correlation noted −0.325, 0.106, < 0.001). PN displayed (14.36 3.18 (21.71 5.82 PP (PFS: 11.98 3.72 months, OS: 20.01 5.18 months). Conclusion underscored prognostic predictive markers uncommon mutations. These biomarkers are crucial achieving informed treatment choices enhancement evaluations this specific group.

Language: Английский

---

Gut microbiota affects PD-L1 therapy and its mechanism in melanoma

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(5)

Published: April 11, 2025

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 blockade, have shown great success in treating melanoma. PD-L1 (B7-H1, CD274), a ligand of PD-1, binds to PD-1 on T cells, inhibiting their activation and proliferation through multiple pathways, thus dampening tumor-reactive cell activity. Studies linked expression melanoma with tumor growth, invasion, metastasis, making the pathway critical target therapy. However, immune-related adverse events are common, reducing effectiveness anti-PD-L1 treatments. Recent evidence suggests that gut microbiome significantly influences anti-tumor immunity, potentially reprogramming microenvironment overcoming resistance anti-PD-1 therapies patients. This review explores mechanisms examines how microbiota its metabolites may help address therapy, offering new insights for improving treatment strategies.

Language: Английский

---

Hyaluronic acid-modified milk exosomes carrying ZNF516 inhibit ABCC5 and contribute to pemetrexed sensitivity in lung adenocarcinoma

Human Cell, Journal Year: 2025, Volume and Issue: 38(3)

Published: April 19, 2025

Language: Английский

---

The potential of targeting autophagy-related non-coding RNAs in the treatment of lung cancer

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 14, 2025

Lung cancer is the most prevalent malignant tumor worldwide and remains leading cause of cancer-related mortality. Despite advances in treatment development, lung patients often face poor quality life low survival rates. Increasing evidence highlights significant roles autophagy non-coding RNAs (ncRNAs) initiation, progression, therapeutic response cancer. Autophagy ncRNAs can function as both tumor-promoting tumor-suppressing factors Therefore, investigating provides valuable insights into its pathophysiology. At same time, RNA also plays an important role regulating autophagy. This study reveals that affects occurrence development through multiple pathways. Then, we studied cancer, (e.g., lncRNAs, miRNAs, circRNAs piRNAs) regulate to promote or inhibit tumorigenesis, metastasis drug resistance Finally, problems solutions were explored. These findings suggest be potential targets for

Language: Английский

---

RIP2/NF-κB/PD-L1 signaling pathway is involved in temozolomide resistance by inducing autophagy in glioblastoma cells

Translational Oncology, Journal Year: 2025, Volume and Issue: 58, P. 102424 - 102424

Published: May 22, 2025

Language: Английский

---

Discovery of a Novel EF24 Analogue-Conjugated Pt(IV) Complex as Multi-Target Pt(IV) Prodrugs Aims to Enhance Anticancer Activity and Overcome Cisplatin Resistance

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Acquired resistance in cancer remains a significant challenge oncology, posing obstacles to the efficacy of diverse therapeutic approaches. The nuclear factor-kappa B (NF-κB) signaling pathway plays an important role development drug tumor cells. Herein, we employed NF-κB inhibitors and cisplatin synthesize multitarget Pt(IV) antitumor prodrugs. Among them, antiproliferation activity complex 8 demonstrated remarkable 146.92-time increase compared against A549/CDDP Moreover, could effectively induce DNA damage, promote ROS generation, autophagy, trigger mitochondrial apoptosis pathway, suppress cell proliferation through pathway. Furthermore, downregulated levels VEGF HIF-1α exerted antiproliferative PI3K/AKT STAT-3 Interestingly, showed superior vivo than cisplatin, 5a, or their combination, suggesting its potential as promising candidate for further lung treatment.

Language: Английский

---

Comprehensive characterization of PD-L1 expression and immunotherapy-related genomic biomarkers in early- versus advanced-stage non-small cell lung cancer

BMC Pulmonary Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: May 7, 2025

Programmed death-ligand 1 (PD-L1) expression is a key biomarker for predicting the efficacy of immune checkpoint inhibitors (ICIs). With successful application perioperative immunotherapy, understanding PD-L1-associated clinical and molecular characteristics in early-stage non-small cell lung cancer (NSCLC) patients essential. We analyzed 3185 NSCLC undergoing targeted next-generation sequencing (NGS) PD-L1 immunohistochemistry (IHC). Associations between profiles were compared across early- (I-III) advanced-stage (IV) cohorts. In (n = 974), high was less common than (lung adenocarcinoma [LUAD]: 7.52% vs. 15.98%, p < 0.001; squamous carcinoma [LUSC]: 18.33% 20.84%, 0.058). For LUAD, more frequent older patients, males smokers. Additionally, LUSC overall showed higher rate LUAD. had lower proportion tumor mutation burden-high (TMB-H) to (p 0.001), but no significant difference observed 0.597). Early-stage also immunotherapy resistance genes (LUAD: 31.15% 48.50%, 0.014; LUSC: 13.64% 45.24%, 0.0067). Moreover, among LUAD with all exhibited significantly different genetic features patients. This study provides comprehensive analysis immunotherapy-related rates offering insights research analysis. Not applicable.

Language: Английский

---