Immunotherapy in Oncogene-Addicted NSCLC: Evidence and Therapeutic Approaches

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 583 - 583

Опубликована: Янв. 11, 2025

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. The discovery specific driver mutations has revolutionized the treatment landscape oncogene-addicted NSCLC through targeted therapies, significantly improving patient outcomes. However, immune checkpoint inhibitors (ICIs) have demonstrated limited effectiveness in this context. Emerging evidence, though, reveals significant heterogeneity among different mutation subgroups, suggesting that certain subsets may benefit from ICIs, particularly when combined with other therapeutic modalities. In review, we comprehensively examine current evidence on efficacy immunotherapy NSCLC. By analyzing recent clinical trials and preclinical studies, along an overview mechanisms reduce efficacy, explored potential strategies to address these challenges, provide insights could optimize approaches integrate them effectively into algorithm for

Язык: Английский

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Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review

Cancers, Год журнала: 2024, Номер 16(13), С. 2338 - 2338

Опубликована: Июнь 26, 2024

Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses utility emerging biomarkers-circulating tumor DNA (ctDNA), microRNAs (miRNAs), blood mutational burden (bTMB)-enhanced by next-generation sequencing (NGS) to improve diagnostic accuracy, prognostic evaluation, strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients 2020 2024, highlights how biomarkers like ctDNA PD-L1 expression critically inform selection personalized therapies, particularly beneficial stages These are critical for assessments dynamically adapting plans, where high specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide use targeted therapies immunotherapies. The findings recommend integrating these into standardized clinical pathways maximize their potential enhancing precision, ultimately fostering significant advancements oncology improving patient outcomes quality life. substantiates predictive value emphasizes need ongoing innovation biomarker research.

Язык: Английский

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer: Current Use and Future Prospects

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 10008 - 10008

Опубликована: Сен. 17, 2024

Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs been developed. Each generation has shown improved effectiveness and fewer effects, resulting in better patient outcomes. For example, patients on gefitinib, first-generation TKI, experienced progression-free survival (PFS) 10 months compared 5 conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib extended PFS 11.1 6.9 cisplatin. Third-generation further increased 38.6 months, 31.8 TKIs. This progress demonstrates ability newer overcome particularly T790M mutation, while adverse effects. Ongoing research focuses overcoming resistance from mutations like C797S improve survival. These developments highlight significant therapy continued effort refine treatment. Recent South Korea shows that third-generation are ineffective against non-small cell lung (NSCLC) mutation. Several trials started showing promising vitro vivo results, but more needed before clinical approval. review underscores notable advancements field EGFR TKIs, offering comprehensive analysis their mechanisms action progression various response resistance.

Язык: Английский

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Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need

Опубликована: Май 3, 2023

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon (10-15% mutations). Predominant types in this category include 18 mutations, 21 L861X, 20 insertions S768I. This group presents a heterogeneous prevalence, partly due the different testing methods presence compound mutation, which some cases leads shorter overall survival TKIs than simple mutations. EGFR-TKI may also vary depending on specific tertiary structure protein. best strategy remains uncertain data efficacy founded few prospective retrospective series. Newer investigational agents still under study there no other approved treatment targeting Defining option for patient population remain un unmet medical need. objective review evaluate existing outcomes, epidemiology clinical characteristics lung cancer patients with rare focus intracranial activity response immunotherapy.

Язык: Английский

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Current status of molecular diagnostics for lung cancer

Exploration of Targeted Anti-tumor Therapy, Год журнала: 2024, Номер 5(3), С. 742 - 765

Опубликована: Июнь 27, 2024

The management of lung cancer (LC) requires the analysis a diverse spectrum molecular targets, including kinase activating mutations in EGFR, ERBB2 (HER2), BRAF and MET oncogenes, KRAS G12C substitutions, ALK, ROS1, RET NTRK1-3 gene fusions. Administration immune checkpoint inhibitors (ICIs) is based on immunohistochemical (IHC) PD-L1 expression determination tumor mutation burden (TMB). Clinical characteristics patients, particularly age, gender smoking history, significantly influence probability finding above targets: for example, LC young patients characterized by high frequency rearrangements, while heavy smokers often have and/or TMB. Proper selection first-line therapy influences overall treatment outcomes, therefore, majority these tests need to be completed within no more than 10 working days. Activating events MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option some laboratories. RNA next-generation sequencing (NGS) capable detecting entire repertoire druggable alterations, therefore it gradually becoming dominating technology diagnosis.

Язык: Английский

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Osimertinib in the Treatment of Epidermal Growth Factor Receptor-Mutant Early and Locally Advanced Stages of Non-Small-Cell Lung Cancer: Current Evidence and Future Perspectives

Cancers, Год журнала: 2025, Номер 17(4), С. 668 - 668

Опубликована: Фев. 16, 2025

The treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients was dramatically revolutionized by the introduction EGFR tyrosine kinase inhibitors in clinical practice, both advanced and locally advanced/early stages. present work focuses on osimertinib use early NSCLC Phase 3 trials have supported as new standard care, adjuvant setting disease. ADAURA study reported an overall survival (OS) advantage for completely resected stage II-IIIA EGFR-mutant tumors, while LAURA proved a statistically significant benefit progression-free (PFS) delay central nervous system metastasis development treated with maintenance after concurrent chemoradiotherapy In neoadjuvant setting, data osimertinib’s efficacy are conflicting; therefore, Neo-ADAURA is evaluating safety alone or combination chemotherapy II-IIIB common mutations. We discuss several issues that need to be clarified, such drug uncommon mutations, long-term impact survival, management resistance mechanisms. Moreover, we report studies trying identify potential biomarkers response, circulating tumor DNA (ctDNA), aim selecting who will most from osimertinib.

Язык: Английский

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Real-World Performance of the EasyPGX® Ready Epidermal Growth Factor Receptor Assay for Genomic Testing of Non-Small Cell Lung Cancer Samples

Biomedicines, Год журнала: 2025, Номер 13(4), С. 814 - 814

Опубликована: Март 28, 2025

Background/Objectives: Activating epidermal growth factor receptor (EGFR) variants is the most common targetable alteration in non-small cell lung cancer (NSCLC). Clinical decision-making requires fast and reliable detection of EGFR early advanced NSCLC, but limited available tissue necessitates tissue-sparing approaches optimized sample management. The objective this study was to assess performance commercial EasyPGX® ready assay using real-world clinical NSCLC samples. Methods: A consecutive cohort 804 non-squamous samples prospectively analyzed with real-time quantitative polymerase chain reaction (RT-qPCR)-based (Diatech Pharmacogenetics, Jesi, Ancona, Italy) compared next-generation sequencing (NGS) assays. Results: NGS revealed conclusive results 99.7% samples, which 11.1% had at least one variant. were exon 19 deletions p.L858R. RT-qPCR-based identified high accuracy (overall concordance rate 94.3%) over a broad range types, variant allele frequencies, tumor contents deoxyribonucleic acid (DNA) input amounts. Conclusions: This demonstrates that valid approach for rapid DNA inputs as low 5 ng (less than 15 recommended by manufacturer), improving management small specimens quantity nucleic acids.

Язык: Английский

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Role of Proteins in Oncology: Advances in Cancer Diagnosis, Prognosis, and Targeted Therapy—A Narrative Review

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(23), С. 7131 - 7131

Опубликована: Ноя. 25, 2024

Modern oncology increasingly relies on the role of proteins as key components in cancer diagnosis, prognosis, and targeted therapy. This review examines advancements protein biomarkers across several types, including breast cancer, lung ovarian hepatocellular carcinoma. These have proven critical for early detection, treatment response monitoring, tailoring personalized therapeutic strategies. The article highlights utility therapies, such tyrosine kinase inhibitors monoclonal antibodies, improving efficacy while minimizing systemic toxicity. Despite these advancements, challenges like tumor resistance, variability expression, diagnostic heterogeneity persist, complicating universal application. underscores future directions, integration artificial intelligence, advanced analysis technologies, development combination therapies to overcome barriers refine treatment.

Язык: Английский

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Saturation resistance profiling of EGFR variants against tyrosine kinase inhibitors using prime editing

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 5, 2023

Abstract Variants of uncertain significance (VUS) hamper the clinical application genetic information. For example, in treating lung cancer with tyrosine kinase inhibitors (TKIs), many epidermal growth factor receptor (EGFR) variants remain classified as VUS respect to TKI sensitivity 1,2 . Such incomplete resistance profiles hinder clinicians from selecting optimal therapeutic agents 3,4 A high-throughput approach that can evaluate functional effects single nucleotide (SNVs) could reduce number VUS. Here we introduce SynPrime, a method based on prime editing enabled generation and evaluation 2,476 SNVs EGFR gene, including 99% all possible canonical domain (exons 18 21). We determined 95% (= 1,726/1,817) protein encoded whole 24) against afatinib, osimertinib, osimertinib presence co-occurring mutation T790M, PC-9 cells. which uses direct sequencing endogenous regions identify SNVs, provided more accurate evaluations than guide RNA abundance-based approach. Our study has potential substantially improve precision choices settings contribute addressing issue by being applied other genes.

Язык: Английский

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Comparative efficacy of targeted therapies and immunotherapy in advanced non-small cell lung cancer: a systematic review

International Journal of Research in Medical Sciences, Год журнала: 2024, Номер 12(9), С. 3384 - 3393

Опубликована: Авг. 12, 2024

Targeted therapies and immunotherapies revolutionized advanced NSCLC treatment outcomes. exploit specific genetic mutations (e.g., EGFR, ALK, BRAF) to inhibit cancer growth while offering significant benefits in progression-free overall survival. therapy drugs for include osimertinib, gefitinib, erlotinib, alectinib, brigatinib, lorlatinib, ceritinib, dabrafenib, trametinib, crizotinib.Resistance side effects like ILD hepatotoxicity cardiovascular issues remain challenges. Immunotherapies with checkpoint inhibitors PD-1, PD-L1, CTLA-4 enhance the immune system's ability body becomes able combat cancer. Drugs pembrolizumab, nivolumab, atezolizumab have shown good efficacy but immune-related adverse a concern. Combination such as e.g., nivolumab ipilimumab can be better option which concerned because these also show promise enhancing

Язык: Английский

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