Effective treatment strategies and key factors influencing therapeutic efficacy in advanced SMARCA4-deficient non-small cell lung cancer DOI Creative Commons
Hui Liu,

Qiyuan Hong,

Shuohan Zheng

et al.

Lung Cancer, Journal Year: 2024, Volume and Issue: 198, P. 108022 - 108022

Published: Nov. 9, 2024

Highlights•First-line local treatment combined with immunotherapy is associated a lower risk of disease progression in locally advanced SMARCA4-deficient NSCLC.•First-line improves survival metastatic NSCLC.•STK11/KEAP1 mutations are linked to reduced efficacy NSCLC.AbstractIntroductionSMARCA4/BRG1-deficient non-small cell lung cancer (SD-NSCLC) high invasiveness and poor prognosis primary resistance standard treatment, especially late-stage patients. This study aimed explore effective treatments identify critical factors impacting therapeutic enhance outcomes for SD-NSCLC patients.Methods103 patients stage III/IV diagnosed by immunohistochemistry from May 2019 March 2024 were included this study. We assessed the patients' clinical genetic features, analyzed according TNM stage, further evaluated efficacy.ResultsIn III patients, no significant differences median progression-free (mPFS) overall (mOS) observed between receiving at site those who did not (p > 0.05), while adding ICIs (immune checkpoint inhibitors) significantly improved mPFS compared non-ICIs (15.0 vs. 7.7 months, p = 0.033), though mOS 0.05). For IV (8.9 4.2 0.006) (19.7 13.1 0.007) treatments. However, among ICIs-treated addition lesion affect Patients STK11/KEAP1 had shorter (3.6 16.2 0.001) (17.7 31.3 0.002), difference was different tumor mutation burden (TMB) PD-L1 expression levels.ConclusionICIs shows promising results SD-NSCLC, first-line SD-NSCLC. may be immunotherapy.

Language: Английский

Management succinate release through SDHA by G protein-coupled receptor 91 signal, TRAP1, and SIRT3 regulation in lung cancer cells by NAR nanoparticles DOI Creative Commons
Eman M. Ragab, Abeer A. Khamis, Tarek M. Mohamed

et al.

Journal of Genetic Engineering and Biotechnology, Journal Year: 2025, Volume and Issue: 23(1), P. 100464 - 100464

Published: Feb. 11, 2025

Language: Английский

Citations

0
Immune Checkpoint Inhibitors and Targeted Therapies in Early-Stage Non-Small-Cell Lung Cancer: State-of-the-Art and Future Perspectives DOI Open Access

Lucrezia Barcellini,

Simone Nardin,

G. Sacco

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 652 - 652

Published: Feb. 14, 2025

Background: Approximately 25-30% of non-small-cell lung cancer (NSCLC) patients are diagnosed when the disease is still resectable, although risk recurrence significant. Recently, approaches based on targeted agents or immune checkpoint inhibitors (ICIs) have modified management such patients. However, some questions remain unanswered. Objectives: Our aim to assess current evidence involving and ICIs in resectable NSCLC, provide an up-to-date overview subject, identify areas debate, Methods: We analyzed randomized trials therapies early-stage published presented at international oncology meetings throughout last 5 years. Results: Osimertinib alectinib shown robust results adjuvant setting for molecularly identified patient subgroups, while achieved data neoadjuvant/perioperative setting, with less consistent pure approach. Circulating tumor DNA levels may offer a possible biomarker therapeutic decisions, albeit more prospective needed. Conclusions: Targeted revolutionizing similarly what was observed advanced disease. Prospective studies designed compare neoadjuvant, adjuvant, perioperative role circulating biomarkers warranted.

Language: Английский

Citations

0
A novel PAK1/TCF1 regulatory axis promotes non-small cell lung cancer progression DOI Creative Commons

Chuangang Lu,

Yingchun Su, Yinghui Xu

et al.

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

Published: March 20, 2025

Non-small cell lung cancer (NSCLC) is the leading cause of death, necessitating identification novel therapeutic targets. P21-activated kinases-1 (PAK1) plays a crucial role in oncogenesis, including NSCLC. Recent findings have elucidated T factor 1 (TCF1) as an anti-tumour factor, influencing biology. However, precise mechanism by which PAK1 promotes NSCLC progression via TCF1 regulation remains unclear. We collected 23 pairs tissue samples and obtained RNA sequencing data corresponding clinicopathologic information from The Cancer Genome Atlas (TCGA). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) immunohistochemistry (IHC) assessed expression tissues cells. Gain loss-of-function experiments evaluated effects on proliferation, invasion, migration, apoptosis vitro. Mechanistically, western blot (WB) immunoprecipitation analysis interaction between Finally, we clinical prognostic, disease progression, immunotherapy response their correlation with immune infiltration, checkpoint inhibitors (PD1, PDL1). was elevated cells, while significantly downregulated. showed significant inverse mRNA Silencing (using shRNAs) inhibiting small molecule IPA-3 suppressed malignancy dose-dependent manner, upregulating expression, vice versa. amplification (TWS119) inhibited invasion manner without affecting expression. Immunoprecipitation confirmed Joint survival indicated that high low were associated unfavourable patients Lastly, correlated infiltration [CD8+ cell, tumor infiltrating lymphocytes (TILs)], PDL1), can accurately predict immunotherapeutic response. This study demonstrates, for first time, negatively regulates TCF1, contributing to pathogenesis. PAK1/TCF1 regulatory axis emerges critical determinant carcinogenesis promising target

Language: Английский

Citations

0
Effective treatment strategies and key factors influencing therapeutic efficacy in advanced SMARCA4-deficient non-small cell lung cancer DOI Creative Commons
Hui Liu,

Qiyuan Hong,

Shuohan Zheng

et al.

Lung Cancer, Journal Year: 2024, Volume and Issue: 198, P. 108022 - 108022

Published: Nov. 9, 2024

Highlights•First-line local treatment combined with immunotherapy is associated a lower risk of disease progression in locally advanced SMARCA4-deficient NSCLC.•First-line improves survival metastatic NSCLC.•STK11/KEAP1 mutations are linked to reduced efficacy NSCLC.AbstractIntroductionSMARCA4/BRG1-deficient non-small cell lung cancer (SD-NSCLC) high invasiveness and poor prognosis primary resistance standard treatment, especially late-stage patients. This study aimed explore effective treatments identify critical factors impacting therapeutic enhance outcomes for SD-NSCLC patients.Methods103 patients stage III/IV diagnosed by immunohistochemistry from May 2019 March 2024 were included this study. We assessed the patients' clinical genetic features, analyzed according TNM stage, further evaluated efficacy.ResultsIn III patients, no significant differences median progression-free (mPFS) overall (mOS) observed between receiving at site those who did not (p > 0.05), while adding ICIs (immune checkpoint inhibitors) significantly improved mPFS compared non-ICIs (15.0 vs. 7.7 months, p = 0.033), though mOS 0.05). For IV (8.9 4.2 0.006) (19.7 13.1 0.007) treatments. However, among ICIs-treated addition lesion affect Patients STK11/KEAP1 had shorter (3.6 16.2 0.001) (17.7 31.3 0.002), difference was different tumor mutation burden (TMB) PD-L1 expression levels.ConclusionICIs shows promising results SD-NSCLC, first-line SD-NSCLC. may be immunotherapy.

Language: Английский

Citations

0