Comprehensive analysis illustrating the role of PANoptosis-related genes in lung cancer based on bioinformatic algorithms and experiments DOI Creative Commons
Shiyou Wei, Zhigang Chen, Xinyu Ling

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 16, 2023

Background: Recently, PANoptosis has aroused the interest of researchers for its role in cancers. However, studies that investigated lung cancer are still few. Methods: The public data were mainly collected from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. R software was utilized analysis data. Quantitative real-time (qRT) polymerase chain reaction (PCR) used to measure RNA level FADD. cell proliferation ability evaluated using CCK8, colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assays. Western blot detect protein specific molecules. Flow cytometry TUNEL staining evaluate apoptosis. Results: In our study, we PANoptosis-related genes previous studies. Through series analysis, identified FADD, an adaptor apoptosis, further analysis. Results showed FADD is one prominent risk factors cancer, localized nucleoplasm cytosol. We next performed immune infiltration biological enrichment illustrate underlying cause cancer. Subsequently, discovered patients with a high might respond worse immunotherapy but better AICAR, bortezomib, docetaxel, gemcitabine. vitro experiments indicated inhibiting could reduce significantly cancerous cells proliferate. Meanwhile, found knockdown promotes apoptosis pyroptosis. Ultimately, prognosis signature based on FADD-regulated genes, which satisfactory prediction efficiency Conclusion: Our result can provide novel direction future focused

Language: Английский

Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial DOI Creative Commons
Martin Schüler, Kristof Cuppens, Till Plönes

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(6), P. 1602 - 1611

Published: April 30, 2024

Abstract Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are standard of care most patients metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses improved event-free survival achieved. New antibody combinations may be more efficacious tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive resectable cancer were randomized to receive two preoperative doses nivolumab (anti-PD-1) without relatlimab (anti-LAG-3) therapy. The primary study endpoint was feasibility surgery within 43 days, which met by all patients. Curative resection achieved 95% Secondary endpoints included pathological radiographic response rates, pathologically complete disease-free overall safety. Major (≤10% viable cells) objective 27% 10% (nivolumab) 30% (nivolumab relatlimab) patients, respectively. 100% 90% tumors lymph nodes completely resected. With 12 months median duration follow-up, rates at 89% 93% (nivolumab), relatlimab). Both treatments safe grade ≥3 treatment-emergent adverse events reported 13% per arm. Exploratory analyses provided insights into biological processes triggered immunotherapy. This establishes safety dual PD-1 LAG-3 surgery. ClinicalTrials.gov Indentifier: NCT04205552 .

Language: Английский

Citations

29
Emerging Targeted Therapies in Non-Small-Cell Lung Cancer (NSCLC) DOI Open Access

Syeda A. Mina,

Mohamed Shanshal, Konstantinos Leventakos

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 353 - 353

Published: Jan. 22, 2025

Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages cancer. Newer advances in common novel oncogenic drivers continue occur at vigorous speed, making it challenging stay up date with rapidly evolving field. In this article, we review emerging perspectives actionable targets We focus on development newer KRAS-directed therapies, particularly non-G12C mutations, pan-RAS inhibitors, RAS-GTP inhibitors. also describe current standard care for EGFR- ALK-altered NSCLC dive into treatments expected be clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, FGFR alterations as Finally, conclude body evidence targeting TROP-2 a target, potentially importance post-targeted therapy scenarios.

Language: Английский

Citations

2
o8G-modified circPLCE1 inhibits lung cancer progression via chaperone-mediated autophagy DOI Creative Commons

Qingyun Zhao,

Dunyu Cai,

Haotian Xu

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 17, 2025

Lung cancer poses a serious threat to human health, but its molecular mechanisms remain unclear. Circular RNAs (circRNAs) are closely associated with tumour progression, and the important role of 8-oxoguanine (o8G) modification in regulating fate RNA has been gradually revealed. However, o8G circRNAs not reported. We identified circPLCE1, which is significantly downregulated lung cancer, further investigated circPLCE1 related mechanism progression. differentially expressed by high-throughput sequencing then conducted methylated immunoprecipitation (MeRIP), immunofluorescence (IF) analysis, crosslinking (CLIP) actinomycin D (ActD) assays explore modification. The biological functions vivo vitro were clarified via establishing silencing/overexpression system. Tagged affinity purification (TRAP), Immunoprecipitation (RIP) coimmunoprecipitation (Co-IP) assays, pSIN-PAmCherry-KFERQ-NE reporter gene used elucidate inhibits This study revealed that reactive oxygen species (ROS) can induce AUF1 mediate decrease stability. found inhibited progression expression was stage prognosis. elucidated: targets HSC70 protein, increases ubiquitination level, regulates ATG5-dependent macroautophagy chaperone-mediated autophagy (CMA) pathway, ultimately o8G-modified through CMA inhibit alter cell fate. provides only new theoretical basis for elucidating also potential treatment. ROS modification, specifically recognizes thereby decreases activity, promotes altering cells inhibiting

Language: Английский

Citations

2
Lung Cancer Treatment Advances in 2022 DOI
Fawzi Abu Rous, Eric K. Singhi, Arthi Sridhar

et al.

Cancer Investigation, Journal Year: 2022, Volume and Issue: 41(1), P. 12 - 24

Published: Aug. 29, 2022

The therapeutic landscape of lung cancer treatment is changing rapidly, and new data was presented at the recently concluded American Society Clinical Oncology 2022 (ASCO22) meeting. We highlight studies clinical relevance that represent significant updates in current management non-small cell (SCLC) small (NSCLC). summarize early-stage NSCLC, mutated non-mutated advanced NSCLC as well (SCLC), discuss these advances context standard care.

Language: Английский

Citations

69
Artificial intelligence-based prediction of clinical outcome in immunotherapy and targeted therapy of lung cancer DOI

Xiaomeng Yin,

Hu Liao,

Yun Hong

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 146 - 159

Published: Aug. 11, 2022

Language: Английский

Citations

64
SMARCA4: Current status and future perspectives in non-small-cell lung cancer DOI Creative Commons

Yumeng Tian,

Lu Xu, Xin Li

et al.

Cancer Letters, Journal Year: 2022, Volume and Issue: 554, P. 216022 - 216022

Published: Nov. 28, 2022

SMARCA4, also known as transcription activator, is an ATP-dependent catalytic subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin-remodeling complexes that participates in the regulation chromatin structure and gene expression by supplying energy. As a tumor suppressor has aberrant ∼10% non-small-cell lung cancers (NSCLCs), SMARCA4 possesses many biological functions, including regulating expression, differentiation transcription. Furthermore, NSCLC patients with alterations have weak response to conventional chemotherapy poor prognosis. Therefore, mechanisms development urgently need be explored identify novel biomarkers precise therapeutic strategies for this subtype. This review systematically describes functions its role development, metastasis, functional epigenetics potential approaches NSCLCs alterations. Additionally, paper explores relationship regulatory shared mutually exclusive SMARCA2. We aim provide innovative treatment improve clinical outcomes

Language: Английский

Citations

54
MET Exon 14 Skipping in NSCLC: A Systematic Literature Review of Epidemiology, Clinical Characteristics, and Outcomes DOI Creative Commons
Julien Mazières,

H. Vioix,

Boris M. Pfeiffer

et al.

Clinical Lung Cancer, Journal Year: 2023, Volume and Issue: 24(6), P. 483 - 497

Published: June 18, 2023

MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with tyrosine kinase inhibitors (TKIs) was recently approved. Given the heterogeneity published data of METex14 NSCLC, we conducted systematic literature review to evaluate its frequency, patient characteristics, and outcomes.On June 13, 2022 publications conference abstracts reporting or outcomes patients NSCLC.We included 139 studies frequency characteristics (350,997 patients), 39 clinical (3989 patients). Median 2.0% unselected minimal geographic variation. 2.4% adenocarcinoma nonsquamous subgroups, 12.0% sarcomatoid, 1.3% squamous histology. Patients NSCLC were more likely be elderly, have histology; there no marked sex smoking status distribution. In first line treatment, median objective response rate ranged from 50.7% 68.8% therapies (both values correspond TKIs), 33.3% immunotherapy, 23.1% 27.0% chemotherapy.Patients are certain but subgroup can ruled out; thus, it crucial test all identify suitable candidates inhibitor therapy. TKIs appeared result higher efficacy outcomes, although direct comparison chemotherapy immunotherapy regimens found.

Language: Английский

Citations

41
Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer DOI Open Access
Shenduo Li,

Guilherme Sacchi de Camargo Correia,

Jing Wang

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 2899 - 2899

Published: May 24, 2023

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung (NSCLC) is most common type and still incurable for patients at advanced stage. Targeted therapy an effective treatment that has significantly improved survival in NSCLC with actionable mutations. However, resistance occurs widely among to disease progression. In addition, many oncogenic driver mutations lack targeted agents. New drugs are being developed tested clinical trials overcome these challenges. This review aims summarize emerging have been conducted or initiated through first-in-human past year.

Language: Английский

Citations

40
Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes DOI Creative Commons
Shideh Mirhadi,

Shirley Tam,

Quan Li

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 5, 2022

Abstract Non-small cell lung cancer (NSCLC) is the leading cause of deaths worldwide. Only a fraction NSCLC harbor actionable driver mutations and there an urgent need for patient-derived model systems that will enable development new targeted therapies. other cancers display profound proteome remodeling compared to normal tissue not predicted by DNA or RNA analyses. Here, we generate 137 xenografts (PDXs) recapitulate histology molecular features primary NSCLC. Proteome analysis PDX models reveals 3 adenocarcinoma 2 squamous carcinoma proteotypes are associated with different patient outcomes, protein-phosphotyrosine profiles, signatures activated pathways candidate targets, in adenocarcinoma, stromal immune features. These findings portend proteome-based classification treatment support resource as viable

Language: Английский

Citations

39
Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance DOI Creative Commons
Taisuke Araki, Shintaro Kanda, Hidehito Horinouchi

et al.

Japanese Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 53(7), P. 547 - 561

Published: June 3, 2023

Abstract Osimertinib, a third-generation EGFR TKI, is the standard therapy for previously untreated EGFR-mutated non-small cell lung cancer patients following landmark FLAURA study. However, resistance inevitably hinders patient prognosis, increasing need new therapeutic strategies beyond osimertinib. Frontline osimertinib-based combination (platinum-based chemotherapy and angiogenesis inhibitors) are currently being tested primarily to prevent initial resistance. In later-line setting after osimertinib, many next-line candidates have been actively examined in clinical trials. Notably, several drugs with novel mechanisms of action, such as antibody–drug conjugates -MET bispecific antibodies, shown promising efficacy despite close application. addition, genotype-based target investigated better understanding osimertinib based on molecular profiling tests at relapse. The C797S mutation MET gene alterations commonly identified resistance, which targeting tested. This review describes current pharmacotherapeutic results trials latest published data, broadly grouped into two sections: 1) TKIs-based front-line 2)

Language: Английский

Citations

39