Immune checkpoint inhibitors in non-small cell lung cancer: from current perspectives to future treatments—a systematic review

Annals of Translational Medicine, Journal Year: 2023, Volume and Issue: 11(10), P. 354 - 354

Published: Aug. 1, 2023

Background: The introduction of immunotherapy in the treatment non-small cell lung cancer (NSCLC) has resulted a radical change patients’ responses and survival rates. increased percentage long survivors, improved toxicity profiles compared to chemotherapy, possible applications for different NSCLC scenarios, have led immune checkpoint inhibitors (ICIs) becoming cornerstone treatment. Therefore, objective this review is describe current future perspectives Methods: A systematic according PRISMA criteria been performed based on clinical trials with from start these treatments until June 2022. Results: use ICIs widespread across both first- second-line anti-PD-1, anti-PD-L1, anti-CTLA-4 drugs. New indications focused adjuvant (atezolizumab) neoadjuvant (nivolumab), now present all stages Given promising results seen trials, new [anti- lymphocyte activation gene-3 (LAG-3) or IDO1] currently under development, will soon be used as standard NSCLC. Conclusions: Immunotherapy mainstay stages, including adjuvant, advanced tumors. development molecules revolutionize coming years.

Language: Английский

---

Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217096 - 217096

Published: July 4, 2024

Language: Английский

---

Cutting-Edge Therapies for Lung Cancer

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 436 - 436

Published: March 1, 2024

Lung cancer remains a formidable global health challenge that necessitates inventive strategies to improve its therapeutic outcomes. The conventional treatments, including surgery, chemotherapy, and radiation, have demonstrated limitations in achieving sustained responses. Therefore, exploring novel approaches encompasses range of interventions show promise enhancing the outcomes for patients with advanced or refractory cases lung cancer. These groundbreaking can potentially overcome resistance offer personalized solutions. Despite rapid evolution emerging therapies, persistent challenges such as resistance, toxicity, patient selection underscore need continued development. Consequently, landscape therapy is transforming introduction precision medicine, immunotherapy, innovative modalities. Additionally, multifaceted approach involving combination therapies integrating targeted agents, immunotherapies, traditional cytotoxic treatments addresses heterogeneity while minimizing adverse effects. This review provides brief overview latest are reshaping treatment. As these progress through clinical trials integrated into standard care, potential more effective, targeted, comes focus, instilling renewed hope facing challenging diagnoses.

Language: Английский

---

Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy

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

Published: Feb. 10, 2025

Over the past decades, significant progress has been made in understanding of non-small cell lung cancer (NSCLC) biology and tumor progression mechanisms, resulting development novel strategies for early detection wide-ranging care approaches. Since their introduction, over 20 years ago, targeted therapies with tyrosine kinase inhibitors (TKIs) have revolutionized treatment landscape NSCLC. Nowadays, remain gold standard many patients, but still they suffer from adverse effects, including unexpected toxicity intrinsic acquired resistance mutations, which lead to relapse. The adoption immune checkpoint (ICIs) 2015, offered exceptional survival benefits patients without targetable alterations. Despite this notable progress, challenges remain, as not all respond favorably ICIs, therapy can develop time. A crucial factor influencing clinical response immunotherapy is microenvironment (TME). TME pivotal orchestrating interactions between neoplastic cells system, growth outcomes. In review, we discuss how intricate relationship success survey current state intervention, a focus on forthcoming promising chimeric antigen receptor (CAR) T sets major obstacles CAR-T therapies, creating conditions that suppress response, inducing exhaustion. To enhance efficacy, specific efforts associated NSCLC, should definitely TME-related immunosuppression escape by combining blockades.

Language: Английский

---

Predictive Biomarkers and Resistance Mechanisms of Checkpoint Inhibitors in Malignant Solid Tumors

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9659 - 9659

Published: Sept. 6, 2024

Predictive biomarkers for immune checkpoint inhibitors (ICIs) in solid tumors such as melanoma, hepatocellular carcinoma (HCC), colorectal cancer (CRC), non-small cell lung (NSCLC), endometrial carcinoma, renal (RCC), or urothelial (UC) include programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), defective deoxyribonucleic acid (DNA) mismatch repair (dMMR), microsatellite instability (MSI), and the microenvironment (TME). Over past decade, several types of ICIs, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, anti-programmed (PD-1) antibodies, anti-lymphocyte activation gene-3 (LAG-3) antibodies have been studied approved by Food Drug Administration (FDA), with ongoing research on others. Recent studies highlight critical role gut microbiome influencing a positive therapeutic response to emphasizing importance modeling factors that can maintain healthy microbiome. However, resistance mechanisms emerge, increased expression alternative checkpoints, T-cell immunoglobulin (Ig), mucin domain-containing 3 (TIM-3), LAG-3, impaired antigen presentation, alterations TME. This review aims synthesize data regarding interactions between microbiota immunotherapy (IT). Understanding these is essential optimizing ICI therapy developing effective combination strategies.

Language: Английский

---

Early-Stage Non-Small Cell Lung Cancer: Prevalence of Actionable Alterations in a Monocentric Consecutive Cohort

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1410 - 1410

Published: April 3, 2024

Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment surgery, but a significant proportion patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has limited clinical benefit. EGFR tyrosine kinase inhibitors immunotherapy have recently opened new therapeutic scenarios. However, only few data are available the ES-NSCLC molecular landscape impact oncogene addiction on therapy definition. Here, we determined prevalence main driver alterations monocentric consecutive cohort. Molecular analysis was performed 1122 cases, including 368 ES 754 advanced NSCLC. actionable similar between early stages. significantly enriched for MET exon-14 skipping presented lower BRAF p.(V600E) mutation. PD-L1 expression levels, evaluated according to alterations, were higher than tumors harboring EGFR, KRAS, gene fusions. Taken together, these results confirm value biomarker testing ES-NSCLC. Although approved targeted therapies still limited, identification could improve patients' selection immunotherapy, favoring enrollment trials allowing faster start at disease

Language: Английский

---

Evidence based on Mendelian randomization: Causal relationship between mitochondrial biological function and lung cancer and its subtypes

Neoplasia, Journal Year: 2023, Volume and Issue: 46, P. 100950 - 100950

Published: Nov. 16, 2023

This study aimed to investigate the causal relationship between mitochondrial biological function and lung cancer, including its subtypes, via MR. SNPs significantly associated with cancer subtypes were employed as instrumental variables. MR-Egger regression, simple mode, weighted median, utilized determine exposure factor occurrence of subtypes. NADH dehydrogenase (ubiquinone) flavoprotein 2 transmembrane protein 70 found have a adenocarcinoma, acting protective factors. The import inner membrane translocase subunit iron-sulfur 4 small-cell was established risk factor. 1 beta subcomplex 8 exhibited Furthermore, NAD-dependent deacylase sirtuin-5 causally linked squamous cell carcinoma, serving A funnel plot demonstrated symmetrical distribution SNPs. Thew pleiotroy test (P > 0.05) "leave-one-out" validated relative stability results.

Language: Английский

---

Differentially Expressed Genes Involved in Primary Resistance to Immunotherapy in Patients with Advanced-Stage Pulmonary Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2048 - 2048

Published: Feb. 8, 2024

In the last few years, nivolumab has become standard of care for advanced-stage lung cancer patients. Unfortunately, up to 60% patients do not respond this treatment. our study, we identified variations in gene expression related primary resistance immunotherapy. Bronchoscopy biopsies were obtained from advanced non-small cell (NSCLC) previously characterized as responders or non-responders after Ten tumor (from three and seven non-responders) analyzed by differential 760 genes using NanoString nCounter platform. These are known be involved response anti-PD1/PD-L1 therapy. All treated with nivolumab. Examining dysregulated 24 made it possible predict Supervised analysis profile (GEP) revealed that responder had significantly higher levels CXCL11, NT5E, KLRK1, CD3G, GZMA, IDO1, LCK, CXCL9, GNLY, ITGAL, HLA-DRB1, CXCR6, IFNG, CD8A, ITK, B2M, HLA-B, HLA-A than did non-responder contrast, PNOC, CD19, TP73, ARG1, FCRL2, PTGER1 lower findings validated predictive biomarkers an independent series 201 (22 hepatocellular carcinomas, 14 non-squamous 5 head neck squamous 1 ureter/renal pelvis carcinoma, 120 melanomas, 4 bladder 31 renal carcinomas). ROC curve showed CD8A best predictors Further, 13/24 adverse impact on overall survival (OS) independent, large NSCLC (2166 cases). summary, found a strong association between global GEP The classification based enabled us identify those who genuinely benefited treatment immune checkpoint inhibitors (ICIs). We also demonstrated abnormal most markers comprising genomic signature influence OS, making them significant therapeutic decision-making. Additional prospective studies larger required confirm clinical utility these biomarkers.

Language: Английский

---

The Role of circHIPK3 in Tumorigenesis and Its Potential as a Biomarker in Lung Cancer

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1483 - 1483

Published: Sept. 4, 2024

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to widely expressed non-small-cell lung (NSCLC) cells, where it plays a crucial role tumorigenesis. CircHIPK3 promotes progression sponging oncosuppressive miRNAs such miR-124, miR-381-3p, miR-149, miR-107, which results increased cell proliferation, migration, resistance therapies. Inhibiting has been demonstrated suppress tumour growth induce apoptosis, suggests its potential use development strategies targeting circHIPK3-related pathways. As biomarker, shows promise for early monitoring cancer. expression levels link metastasis risk highlights clinical relevance. Given preliminary findings, more trials are needed validate efficacy biomarker. Moreover, future research should determine if mechanisms discovered NSCLC apply small (SCLC) investigate circHIPK3-targeted therapies SCLC.

Language: Английский

---

Computational analysis of whole slide images predicts PD-L1 expression and progression-free survival in immunotherapy-treated non-small cell lung cancer patients

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 6, 2025

Language: Английский

---