Lung Cancer: Targets and Therapy最新文献

{"title":"Tiered Group of Disease Driven Oncogene Informs Survival Outcome of Taiwanese and Japanese Patients with Advanced NSCLC in the LC-SCRUM-Asia Study.","authors":"Chih-Hsi Scott Kuo, Shigeki Umemura, Chin-Chou Wang, Shingo Matsumoto, How-Wen Ko, Fu-Tsai Chung, Ping-Chih Hsu, Hiroki Izumi, Yuji Shibata, Hibiki Udagawa, Kiyotaka Yoh, Yuri Murata, Koichi Goto, Cheng-Ta Yang","doi":"10.2147/LCTT.S631512","DOIUrl":"10.2147/LCTT.S631512","url":null,"abstract":"<p><strong>Background: </strong>Targeted therapy improves survival of oncogene-driven NSCLC. We evaluate the clinical outcome of advanced NSCLC with oncogenic drivers in LC-SCRUM-Asia Taiwanese and Japanese cohort using tiered groups of disease-driven oncogene.</p><p><strong>Methods: </strong>Fourteen genes were reported from NGS and grouped into four tiers based on lines of approved targeted therapies in Taiwan and Japan (Tier 1: ≥ two lines; Tier 2: one line; Tier 3: not targetable; Tier 4: potentially targetable; not yet approved). Overall survival (OS) of the four-tier gene groups was analyzed in Taiwanese cohort and validated in the 8619 Japanese patients using a two-stage approach.</p><p><strong>Results: </strong>Three-hundred-fifty-nine patients were enrolled in Taiwanese cohort, of which 249 (69.4%) patients had a reported genomic alteration. Patients with a history of smoking (HR 0.46 [95% CI, 0.23-0.92]; p=0.031) and squamous cell carcinoma (HR 0.31 [95% CI, 0.12-0.78]; p=0.014) had a lower incidence of genomic alterations. The top five genomic alterations were <i>EGFR</i> (44.6%),<i> KRAS</i> (7.2%),<i> ALK</i> (3.9%),<i> MET</i> (3.1%) and <i>ERBB2</i> (2.5%) mutations. The four-tier gene groups were significantly associated with different OS in Taiwanese patients (Log rank test <i>p</i> < 0.001). The adjusted OS was the longest and the shortest in patients with Tier 1 (34.5 months) and Tier 4 (16.6 months) gene groups, respectively. In Japanese cohort, a similar trend between the four-tier gene groups and OS was observed (Log rank test p < 0.001) where the Tier 1 and the Tier 4 gene groups also demonstrated the longest (42.6 months) and the shortest OS (18.9 months), respectively.</p><p><strong>Conclusion: </strong>The available lines of targeted therapy impact survival in patients of advanced oncogene-driven NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"631512"},"PeriodicalIF":3.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can We Extend Beyond 2 Years of Adjuvant ALK TKI Established by ALINA and ELEVATE in Resected Early Stage <i>ALK+</i> NSCLC a Disease with High Predilection for CNS Metastasis with Novel Clinical Trial Designs?","authors":"Vivian Thuy Tieu, Misako Nagasaka, Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S642874","DOIUrl":"https://doi.org/10.2147/LCTT.S642874","url":null,"abstract":"<p><p>The development and approval of three generations of ALK tyrosine kinase inhibitors (TKIs) since the identification of anaplastic lymphoma kinase fusions (<i>ALK+</i>) in NSCLC has led to improved survival especially with lorlatinib, the only third-generation ALK TKI in the metastatic incurable stage. The establishment of 3 years of adjuvant EGFR TKI in resected stage IB-IIIA EGFR+ NSCLC has led to improvement in overall survival (OS) when compared to placebo. Logically, the use of adjuvant ALK TKI in resected early-stage <i>ALK+</i> NSCLC has been investigated. But instead of three years of adjuvant TKI, in line with EGFR+ and RET+ NSCLC, the use of ALK TKI was investigated for only 2 years in both ALINA and ELEVATE trials. Unsurprisingly, alectinib (ALINA trial) and ensartinib (ELEVATE trial), respectively, has led to improved disease-free survival (DFS) so far with OS follow up on-going. Nonetheless, this is a disease that requires constant tumor suppression to prevent or delay CNS metastasis, as exemplified by the CNS data from the 7-year CROWN update. In addition, to reviewing the results of ALINA and ELEVATE, we propose two alternate novel clinical designs to build upon the 2-years of adjuvant 2G ALK TKIs.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"642874"},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healing of Post-Operative Tracheal Disruption in a Patient with Thymic Carcinoma on Adjuvant Immunotherapy.","authors":"Jessica Lubisich, Hari B Keshava, Jeremy P Harris, Tjoson Tjoa, Cathleen J Park, Zhaohui L Arter, Sai-Hong Ignatius Ou, Misako Nagasaka","doi":"10.2147/LCTT.S625383","DOIUrl":"10.2147/LCTT.S625383","url":null,"abstract":"<p><p>Pneumomediastinum from tracheal perforations due to primary repair breakdown can occur as a complication of thymic cancer surgery. Immunotherapy may be a viable adjuvant treatment for thymic carcinoma patients with tracheal perforations.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"625383"},"PeriodicalIF":3.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149062091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of JAML as an Immune-Associated Prognostic Marker in Non-Small Cell Lung Cancer.","authors":"Qin Tian, Fucheng Zhang, Chunyan Han","doi":"10.2147/LCTT.S616193","DOIUrl":"10.2147/LCTT.S616193","url":null,"abstract":"<p><strong>Introduction: </strong>Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality worldwide, and the identification of novel prognostic biomarkers associated with tumor immunity is urgently needed. Junctional adhesion molecule-like (JAML), a member of the junctional adhesion molecule family, participates in leukocyte adhesion, migration, and T-cell activation. Although JAML has been implicated in immune regulation and tumor progression in other cancers, its expression pattern, prognostic significance, and association with the immune microenvironment in NSCLC remain unclear. This study aimed to investigate the clinical and immunological significance of JAML in NSCLC.</p><p><strong>Methods: </strong>Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to evaluate JAML expression patterns in NSCLC subtypes. The prognostic value of JAML was assessed using Kaplan-Meier survival analysis and Cox regression models. The association between JAML expression and immune cell infiltration was investigated using TIMER2.0, CIBERSORT, and TISIDB analyses. Functional enrichment analyses were performed to explore potential biological pathways associated with JAML expression. In addition, JAML expression was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paired NSCLC and adjacent normal tissues.</p><p><strong>Results: </strong>JAML expression was significantly decreased in NSCLC tissues compared with normal tissues (P < 0.005), with the lowest expression observed in lung squamous cell carcinoma (LUSC) and reduced expression in lung adenocarcinoma (LUAD). Survival analysis demonstrated that patients with high JAML expression had significantly improved overall survival compared with those with low expression (univariate HR = 0.68, 95% CI: 0.54-0.86, P = 0.001; multivariate HR = 0.76, 95% CI: 0.57-1.00, P = 0.049). Immune infiltration analysis revealed that JAML expression was significantly associated with multiple immune cell populations, including CD8+ T cells (r = 0.42, P < 0.001), suggesting a close relationship between JAML expression and the tumor immune microenvironment. qRT-PCR validation confirmed that JAML expression was approximately 2.3-fold higher in adjacent normal tissues than in NSCLC tissues (P < 0.05).</p><p><strong>Conclusion: </strong>JAML is downregulated in NSCLC and its high expression is associated with favorable overall survival and distinct immune infiltration patterns. These findings indicate that JAML may serve as a potential prognostic biomarker and provide insights into the relationship between JAML expression and the tumor immune microenvironment in NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"616193"},"PeriodicalIF":3.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unilateral Scleral Icterus as a Rare Presentation of Choroidal Metastasis in Transdifferentiated EGFR-Mutant Lung Cancer: A Case Report and Review of the Literature.","authors":"Oz Levinkron, Thubeena Manickavasagar, Sanjay Popat, Richard Scawn","doi":"10.2147/LCTT.S604360","DOIUrl":"10.2147/LCTT.S604360","url":null,"abstract":"<p><p>Unilateral scleral icterus is an extremely rare clinical finding and is not typically associated with systemic hyperbilirubinemia. We report the case of a 28-year-old man with biopsy-proven transdifferentiated neuroendocrine lung carcinoma arising from EGFR-mutant non-small cell lung cancer (NSCLC), who presented with painless, localized yellow discoloration of the temporal sclera of the right eye without systemic features of jaundice. Ophthalmic examination revealed reduced visual acuity in the affected eye and an elevated temporal chorio-retinal mass. B-scan ultrasonography demonstrated a dome-shaped lesion measuring 6 mm in thickness with moderate internal reflectivity. Laboratory investigations, including serum bilirubin and liver enzymes, were normal, and systemic imaging showed no hepatic or biliary pathology. The patient was diagnosed with choroidal metastasis and treated with urgent external beam radiotherapy followed by systemic chemotherapy. The unilateral scleral icterus was attributed to localized xanthochromic changes related to the choroidal metastasis. This case highlights unilateral scleral icterus as a rare ocular sign of choroidal metastasis. To our knowledge, this is the first reported case in which choroidal metastasis-specifically from transdifferentiated neuroendocrine lung carcinoma-presented with unilateral scleral yellowing. Previously published cases of unilateral scleral icterus have been associated with subconjunctival or suprachoroidal hemorrhage, prior ocular surgery, localized facial malignancy, or treatment-related vascular changes rather than metastatic infiltration. This report expands the differential diagnosis of unilateral scleral discoloration and underscores the importance of prompt ophthalmologic evaluation in oncology patients with new ocular findings, even in the absence of visual symptoms or biochemical evidence of jaundice. It also emphasizes the value of multidisciplinary collaboration between ophthalmology and oncology in recognizing atypical manifestations of advanced malignancy.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"604360"},"PeriodicalIF":3.3,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sunvozertinib in EGFR Exon 20 Insertion NSCLC: Approved but Not Available - Practical Dose Selection Considerations and Real-World Access Challenges.","authors":"Kim Abbegail Tan Aldecoa, Zhaohui Liao Arter, Sai-Hong Ignatius Ou, Misako Nagasaka","doi":"10.2147/LCTT.S592922","DOIUrl":"10.2147/LCTT.S592922","url":null,"abstract":"<p><p>Sunvozertinib has emerged as one of the most promising tyrosine kinase inhibitors (TKIs) for previously treated non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutations, a molecular subset with limited sensitivity to conventional EGFR TKIs and a persistent unmet need especially in the second-line setting. Regulatory approvals have occurred at different doses - 300 mg daily in China based on WU-KONG6 and 200mg daily in the United States based on WU-KONG1B - raising an important question regarding optimal dose selection in clinical practice. In this editorial, we outline the preclinical and clinical evidence supporting sunvozertinib's approval, compare the efficacy and tolerability at 200mg versus 300mg, and discuss other emerging TKIs in this evolving treatment landscape. Finally, we highlight a critical paradox: despite FDA approval, sunvozertinib remains largely inaccessible to patients in the United States.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"592922"},"PeriodicalIF":3.3,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Selpercatinib in a <i>CCDC6-RET</i> Lung Adenocarcinoma with an Acquired Novel <i>RET</i> p.L730_G731insL After Progression on Pralsetinib: A Case Report.","authors":"Chunyu Tian, Yang Zou, Jinxin Liu, Jing Zhao, Simiao Tian, Ying Liu, Gang Wang","doi":"10.2147/LCTT.S605845","DOIUrl":"10.2147/LCTT.S605845","url":null,"abstract":"<p><p><i>RET</i> fusion is one of the key driver oncogenes in lung cancer. Selective <i>RET</i> inhibitors have become the standard of care for these patients. However, acquired resistance remains inevitable Among the mechanisms of on-target resistance, solvent front mutations in the <i>RET</i> kinase domain are the most common. In contrast, kinase domain insertion mutations are rarely reported as a mechanism of resistance. This article reports a case of a patient with advanced lung adenocarcinoma. Initial genetic testing at diagnosis revealed a <i>CCDC6-RET</i> fusion. The patient achieved partial response after treatment with pralsetinib, but subsequently developed disease progression. After resistance developed, next-generation sequencing (NGS) was performed. The results showed that the original <i>RET</i> fusion persisted. Additionally, a newly acquired insertion mutation (p.L730_G731insL) was detected in the <i>RET</i> kinase domain. Based on this resistance mechanism, the patient discontinued pralsetinib. Treatment was switched to another selective <i>RET</i> inhibitor, selpercatinib. Follow-up imaging evaluation showed that the pulmonary lesions achieved a partial response (PR).This suggests that selpercatinib has therapeutic activity against the tumor carrying this <i>RET</i> insertion mutation. However, the patient received concurrent brain radiotherapy and radiofrequency ablation of liver lesions; therefore, the response in intracranial and hepatic sites cannot be solely attributed to selpercatinib. The observation is hypothesis-generating rather than proof of sensitivity. This case provides a reference for precision treatment strategies after resistance to <i>RET</i> inhibitors.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"605845"},"PeriodicalIF":3.3,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2-ADC and HER2-TKI Overcomes HER2 Amplification as an Acquired Resistance to Zongertinib - A Case Report.","authors":"Misako Nagasaka, Zhaohui L Arter, Cathleen J Park, Akshat Sarkari, Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S600499","DOIUrl":"10.2147/LCTT.S600499","url":null,"abstract":"<p><p>Trastuzumab deruxtecan, zongertinib and sevabertinib have been approved in the United States for the treatment of patients with advanced metastatic HER2 mutated non-small-cell lung cancer (NSCLC). Unfortunately, tumor progression is inevitable in many cases. In this case report, we share our experience with a patient with HER2 mutated NSCLC who responded to the combination of trastuzumab deruxtecan and zongertinib after progressing on each agent when given alone, highlighting the potential for such combinations.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"600499"},"PeriodicalIF":3.3,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory Identification of Gene Copy Number Cut-Off for NGS-Based <i>MET</i> Amplification Assessment and Clinical Relevance to MET Inhibitor Outcomes in Non-Small-Cell Lung Cancer.","authors":"Si-Yang Maggie Liu, Zhi Xie, Lixu Yan, Guang-Ling Jie, Jia-Yi Deng, Qingling Zhang, Zhan Huang, Jin Wang, Zhou Zhang, Yang Shao, Hao Meng, Yan Zhang, Xu-Chao Zhang, Hua-Jun Chen, Wen-Zhao Zhong, Qing Zhou, Yi-Long Wu","doi":"10.2147/LCTT.S596080","DOIUrl":"10.2147/LCTT.S596080","url":null,"abstract":"<p><strong>Introduction: </strong><i>MET</i> amplification is a critical oncogenic driver and a major mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC). Currently, next-generation sequencing (NGS)-based assays are increasingly used in clinical practice. However, they lack a unified standard for defining MET amplification across multiple NGS platforms with a potential actionable threshold.</p><p><strong>Methods: </strong>This was a multiple-site joint study to optimize the cut-off value for <i>MET</i> amplification using tumor tissue and NGS analysis. In the training cohort, five NGS panels were used to detect <i>MET</i> gene copy number (GCN), and fluorescence in situ hybridization (FISH) was used as a reference. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff with 100% specificity and 66.7% sensitivity. The results were validated in an independent cohort to explore the correlation between <i>MET</i> amplification and efficacy of MET inhibitors in patients with NSCLC.</p><p><strong>Results: </strong>In the training cohort (n=21), the optimal <i>MET</i> GCN cut-off was determined to be 6.55, yielding an area under the curve of 0.9, corresponding to an accuracy of 85.7%. <i>MET</i> polysomy, identified using FISH (n=2), was also detected using NGS. All five NGS panels demonstrated good concordance with FISH, with accuracies ranging from 75.0% to 85.7%. In the validation cohort (n=29), NGS analysis demonstrated a good performance, with an accuracy rate of 79.3%. Patients with <i>MET</i> GCN ≥ 6.55 had a significantly longer median progression free survival than those with <i>MET</i> GCN < 6.55 (hazard ratio = 0.42; p = 0.03).</p><p><strong>Conclusion: </strong>In this study, an exploratory cut-off of 6.55 for <i>MET</i> GCN by NGS was associated with <i>MET</i> amplification and longer progression-free survival in patients receiving targeted therapy. However, given the retrospective design and limited sample size, these findings should be regarded as exploratory and require validation in larger, prospective cohorts before broader clinical application.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"596080"},"PeriodicalIF":3.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13165478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficiency of Immunological Blood Biomarkers in Predicting Chemotherapy Response and Survival Outcome for Non-Targetable Advanced Non-Small Cell Lung Cancer Patients.","authors":"Putthapoom Lumjiaktase, Nanthisa Kemawichanurat, Kanthon Santiwiwas, Thatchathum Kuttiyod, Songporn Oranratnachai, Narumol Trachu, Nanamon Monnamo, Khantong Khiewngam, Kantapat Simmalee, Thanyanan Reungwetwattana","doi":"10.2147/LCTT.S578622","DOIUrl":"10.2147/LCTT.S578622","url":null,"abstract":"<p><strong>Purpose: </strong>Chemotherapy is the main therapy for non-targetable advanced non-small cell lung cancer (NSCLC). Nevertheless, few biomarkers are currently available for predicting clinical outcomes and monitoring treatment response.</p><p><strong>Patients and methods: </strong>The blood samples of 42 patients with non-targetable advanced NSCLC who received chemotherapy were collected before chemotherapy and after chemotherapy. The circulating immune cells and subpopulation Treg were investigated using flow cytometry, and human immune checkpoint biomarker levels were analysed by multiplex bead-based assay.</p><p><strong>Results: </strong>After selecting the effective biomarkers for survival analysis, high pre-chemotherapy sCD25 (≥499.52 pg/mL; 4.52 vs 14.98 months, p = 0.030) and post-chemotherapy (≥515.23 pg/mL; 3.90 vs 21.25 months, p = 0.004) were associated with poorer median progression-free survival (PFS). An increase in pre-chemotherapy neutrophil to lymphocyte ratio (NLR) (ratio ≥ 6.9; 5.15 vs 21.54 months, p = 0.008) and post-chemotherapy NLR (ratio ≥ 3.1; 10-month OS 50.35% vs 83.57%, p = 0.014) was correlated with shorter overall survival (OS). Moreover, increased pre-chemotherapy %NKT cells (≥6.8%) were linked to improved clinical benefit rate (CBR) (2.72 vs 3.97 months, p = 0.013), while higher post-chemotherapy %NK cells (≥23.1%) were associated with rapid overall response rate (ORR) at 4 months (82.05% vs 25%, p = 0.035).</p><p><strong>Conclusion: </strong>Our findings suggest that sCD25 and NLR show potential as indicators of PFS and OS, respectively. Additionally, pre-chemotherapy %NKT and post-chemotherapy %NK cells may provide insight into monitoring chemotherapy response. This pilot study identified potential candidate biomarkers for further investigation to confirm their clinical utility.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"17 ","pages":"578622"},"PeriodicalIF":3.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}