Lung Cancer最新文献

{"title":"Long-term outcomes of Extensive-Stage small cell lung cancer treated with chemotherapy or Chemo-immunotherapy: A propensity score adjusted cohort study","authors":"Heya Batah ,&nbsp;Emily C. Zabor ,&nbsp;Bridget Adcock ,&nbsp;Monica Lee ,&nbsp;Preeyal Patel ,&nbsp;Meera Patel ,&nbsp;Hadil Zureigat ,&nbsp;Ahmed Nabil Mohamed ,&nbsp;Daniel Paul Nurse ,&nbsp;Yohanna B. Bedelu ,&nbsp;Jacqulyn Tomer ,&nbsp;Lukas Delasos ,&nbsp;Khaled A. Hassan ,&nbsp;Nathan A. Pennell ,&nbsp;Marc A. Shapiro ,&nbsp;James Stevenson ,&nbsp;Alex A. Adjei ,&nbsp;Moaath Khader Mustafa Ali","doi":"10.1016/j.lungcan.2025.108847","DOIUrl":"10.1016/j.lungcan.2025.108847","url":null,"abstract":"<div><h3>Background</h3><div>Combining atezolizumab with carboplatin plus etoposide (Carbo-E) improved overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). However, there is a paucity of real-world outcomes. We present the largest and longest follow-up retrospective study evaluating treatment outcomes in ES-SCLC.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study to compare response rate, OS, and progression-free survival (PFS) in patients with ES-SCLC who received Carbo-E, Carbo-E and atezolizumab (Carbo-E-Atezo), and cisplatin and etoposide (Cis-E). We included all adult patients (≥ 18 years) treated at Cleveland Clinic between 1/2010–12/2022. Propensity score (PS) weighting and multivariable Cox proportional hazards regression adjusted for confounders.</div></div><div><h3>Results</h3><div>Among 602 ES-SCLC patients, 375 (62 %) received Carbo-E, 160 (27 %) received Carbo-E-Atezo, and 67 (11 %) received Cis-E. The median age was 67, 65, and 59 years, respectively. The median follow-up among survivors was 23.9 months (IQR: 13.3–––57.3). Five-year unadjusted OS was 4.5 % (Carbo-E), 7 % (Carbo-E-Atezo), and 5.2 % (Cis-E). Carbo-E-Atezo was associated with a longer PS-adjusted median OS than Carbo-E (9.1 vs. 8.2 months, P = 0.039), but no difference was seen in PFS (5.5 vs. 5.5, P = 0.09) or response rate (P &gt; 0.9). Compared to Carbo-E, Cis-E showed higher response rates (OR: 1.67, P = 0.03) but no improvement in OS (11 vs 8.3 months, P = 0.067) or PFS (7.7 vs. 5.5 months, P = 0.058). Cis-E did not differ significantly from Carbo-E-Atezo in response rate, OS, or PFS.</div></div><div><h3>Conclusion</h3><div>Long-term outcomes in ES-SCLC remain poor. Atezolizumab added to Carbo-E modestly improved OS but not PFS. Cisplatin-based regimens increased response rates but did not improve survival.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108847"},"PeriodicalIF":4.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reappraising preoperative ctDNA in EGFR-mutant NSCLC: from detection to responsible clinical integration","authors":"Man Sun ,&nbsp;Dan Zang ,&nbsp;Jun Chen","doi":"10.1016/j.lungcan.2025.108846","DOIUrl":"10.1016/j.lungcan.2025.108846","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108846"},"PeriodicalIF":4.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tarlatamab population survival kinetics in extensive-stage small cell lung cancer: brief report","authors":"David J. Stewart ,&nbsp;Bingnan Zhang ,&nbsp;Razelle Kurzrock","doi":"10.1016/j.lungcan.2025.108844","DOIUrl":"10.1016/j.lungcan.2025.108844","url":null,"abstract":"<div><h3>Purpose</h3><div>Immune checkpoint inhibitors (ICIs) prolong progression-free survival (PFS) and overall survival (OS) in extensive-stage small cell lung cancer (ES-SCLC). ES-SCLC PFS curve exponential decay nonlinear regression analyses (EDNLRAs) suggests that only 10% of patients benefit. Here we report ES-SCLC EDNLRAs for the bispecific T-cell engager tarlatamab.</div></div><div><h3>Experimental design</h3><div>We digitized tarlatamab ES-SCLC PFS and OS curves from published studies and performed EDNLRAs of curve data.</div></div><div><h3>Results</h3><div>All four PFS curves fit 2-phase decay models, suggesting the presence of two distinct subpopulations- one with a short PFS half-life (median 3.2 months, similar to the tarlatamab DeLLphi-304 study chemotherapy arm) and the other with a very long PFS half-life). EDNLRAs indicated that 88 % of the patients belonged to the rapidly progressing subpopulation. The proportion of patients in the subpopulation with long PFS was lower than the study response rates. However, log-linear plots of response-duration curves also suggested 2-phase decay, with one subpopulation having very long responses and the other having very short responses. Two of four OS curves assessed fit 2-phase decay models. Longer follow-up will be required to assess the other two curves. For curves fitting 2-phase decay models, OS half-life for the subpopulation with shorter OS was modestly longer than the OS for the Dellphi-304 chemotherapy arm.</div></div><div><h3>Conclusions</h3><div>In ES-SCLC, EDNLRA of tarlatamab PFS curves and log-linear plots of response duration curves suggest two distinct subpopulations- one deriving marked benefit from tarlatamab and the other deriving much less benefit. Individual patient data might provide insight into underlying driving factors.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108844"},"PeriodicalIF":4.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and molecular landscape of NRG1 fusions in Japanese solid tumors: a nationwide data analysis using the C-CAT database","authors":"Masaki Ishida ,&nbsp;Tadaaki Yamada ,&nbsp;Ryo Tsunashima ,&nbsp;Midori Morita ,&nbsp;Nobutaka Kataoka ,&nbsp;Yusuke Kunimatsu ,&nbsp;Ryo Sawada ,&nbsp;Tae Hata ,&nbsp;Hayato Kawachi ,&nbsp;Masahiro Iwasaku ,&nbsp;Yasuto Naoi ,&nbsp;Koichi Takayama","doi":"10.1016/j.lungcan.2025.108843","DOIUrl":"10.1016/j.lungcan.2025.108843","url":null,"abstract":"<div><h3>Introduction</h3><div>Neuregulin 1 (<em>NRG1</em>) gene fusions are critical oncogenic drivers that activate the ERBB signaling pathway across various solid tumors. Although targeted therapies for <em>NRG1</em> fusion-positive cancers are advancing rapidly in clinical settings, their epidemiological and clinicogenomic characteristics remain poorly understood, warranting large-scale investigations.</div></div><div><h3>Methods</h3><div>We performed a retrospective analysis of patients with advanced solid tumors who were registered in the Center for Cancer Genomics and Advanced Therapeutics database of Japan between June 2019 and February 2025. Our evaluation focused on the prevalence of <em>NRG1</em> fusions, identities of fusion partners, co-occurring genomic alterations, tumor mutational burden, microsatellite instability status, and relevant clinical characteristics.</div></div><div><h3>Results</h3><div>Our study included 95,149 patients with advanced solid tumors who underwent comprehensive genomic profiling. Among them, 29 (0.03 %) harbored <em>NRG1</em> fusions, most frequently in lung cancer (17 of 5,670 cases, 0.30 %). CD74 emerged as the predominant fusion partner, constituting 82.4 % of lung cancers, whereas other solid tumors exhibited a more diverse range of partners. Co-occurring genomic alterations were detected in 20 of 29 patients (69.0 %), with the most frequent alterations found in <em>CDKN2A</em>, <em>CDKN2B</em>, and <em>MTAP</em>. Additionally, pathological examination revealed mucinous adenocarcinoma in 17.6 % of lung cancers associated with <em>NRG1</em> fusions.</div></div><div><h3>Conclusion</h3><div>This study confirms that <em>NRG1</em> fusions are rare but significantly associated with lung cancer and the CD74 fusion partner. Our nationwide analysis represents the most comprehensive assessment of <em>NRG1</em> fusions in Japanese patients with advanced solid tumors.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108843"},"PeriodicalIF":4.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment and outcomes of limited stage small cell lung cancer in the Canadian small cell lung cancer database (CASCADE)","authors":"William J. Phillips ,&nbsp;Luna Jia Zhan ,&nbsp;Deepro Chowdhury ,&nbsp;Jeniszka Gill ,&nbsp;Alexander Sun ,&nbsp;Rebekah Rittberg ,&nbsp;Victor Cohen ,&nbsp;Amanda J.W. Gibson ,&nbsp;Michael Yan ,&nbsp;Daniel Liwski ,&nbsp;Saritha Surapaneni ,&nbsp;Marie Frederique D’Amours ,&nbsp;Fabian P.S. Yu ,&nbsp;YongJin Kim ,&nbsp;Rana A. Qadeer ,&nbsp;David E. Dawe ,&nbsp;Jason Agulnik ,&nbsp;Vishal Navani ,&nbsp;Andrea S. Fung ,&nbsp;Stephanie Snow ,&nbsp;Sara Moore","doi":"10.1016/j.lungcan.2025.108840","DOIUrl":"10.1016/j.lungcan.2025.108840","url":null,"abstract":"<div><h3>Introduction</h3><div>There have been minimal advances in the systemic treatment of limited stage small cell lung cancer (LS-SCLC) for decades. With the publication of the ADRIATIC trial, consolidation durvalumab is a new standard of care. This study evaluated real-world treatments and clinical outcomes prior to the era of immunotherapy for LS-SCLC.</div></div><div><h3>Methods</h3><div>The Canadian Small Cell Lung Cancer Database (CASCADE) is a Canadian multi-institutional federated database that includes patients with SCLC from 9 academic institutions. This analysis included patients with pathologically confirmed LS-SCLC treated curatively between January 2001 and December 2022. Baseline characteristics and treatment patterns were obtained from medical records and assessed descriptively. The primary outcome was overall survival (OS) assessed using Kaplan Meier (KM) methods. OS was also assessed among patients who received treatment eligible for participation in the ADRIATIC trial.</div></div><div><h3>Results</h3><div>A total of 1,024 patients were included. Median age was 66 years old and 52 % of patients were female. Concurrent chemoradiation therapy (cCRT) was the most common treatment modality (76 %), followed by surgery (11 %) and sequential CRT (10 %). Median OS was 24.9 months (95 % confidence interval [CI] = 23.4–27.4). Only 36 % of patients treated with cCRT received treatment meeting eligibility criteria for the ADRIATIC trial. The most common reason for ineligibility was due to the radiation therapy (RT) dose/schedule used. Median OS of eligible and ineligible patients was 30.3 months (95 % CI = 26.4–36.4) versus 21.7 months (95 % CI = 19.7–24.9).</div></div><div><h3>Conclusions</h3><div>Survival outcomes for LS-SCLC remain poor despite curative-intent multimodality treatment. Immunotherapy represents a promising advance but a high proportion of patients in the real-world receive treatment that was not represented in the ADRIATIC trial. Future work evaluating the outcomes of patients treated with immunotherapy is critical to assess its real-world impact.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108840"},"PeriodicalIF":4.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic composition and evolutionary trajectories of brain metastasis in non-small-cell lung cancer","authors":"Marcin Nicoś ,&nbsp;Natalia Galant ,&nbsp;Anna Kowalczyk ,&nbsp;Rafał Pęksa ,&nbsp;Bożena Jarosz ,&nbsp;Monika Żuk ,&nbsp;Bartosz Wasąg ,&nbsp;Renata Duchnowska ,&nbsp;Paweł Krawczyk ,&nbsp;Jacek Jassem ,&nbsp;Nicola Crosetto","doi":"10.1016/j.lungcan.2025.108842","DOIUrl":"10.1016/j.lungcan.2025.108842","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-small cell lung cancer (NSCLC) is an aggressive solid malignancy that commonly disseminates to the central nervous system (CNS). Comparative analysis of primary NSCLC and brain metastases (BM) by next-generation sequencing may reveal somatic genetic alterations that drive or favor NSCLC-derived BM.</div></div><div><h3>Methods</h3><div>We performed whole-exome sequencing (WES) in 62 archival samples from 31 paired-matched primary NSCLC sites and corresponding BM. The median age of patients was 66 years; 22 had adenocarcinoma, and 9 had squamous cell carcinoma, 6 patients presented synchronous BM at lung cancer diagnosis, and 22 developed BM after 1–78 months (median 13 months).</div></div><div><h3>Results</h3><div>Mutations in the <em>RTK-RAS</em>, WNT, NOTCH, and <em>PIK</em> pathways were enriched across all samples. The <em>KMT2D</em> and <em>TP53</em> genes were the most frequently mutated in the primary tumor and corresponding BM. <em>FAT1</em>, <em>NSD1</em>, and <em>NF1</em> mutations were among the most frequent alterations newly detected in BM. Non-druggable hotspot alterations in actionable genes, including <em>EGFR</em>, <em>KRAS</em>, <em>ALK</em>, and <em>ROS1</em>, showed various patterns between the two tumor sites.</div></div><div><h3>Conclusions</h3><div>Our study provides a comprehensive overview of genetic alterations specific to primary NSCLC, unique to BM, and shared between both sites, which may contribute to BM formation affecting various evolutionary trajectories.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108842"},"PeriodicalIF":4.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of N1 lymph node burden on survival outcomes in non-skip pN2 non-small-cell lung cancer","authors":"Bin Luo ,&nbsp;Shenhua Liang ,&nbsp;Leqi Zhong ,&nbsp;Wuyou Gao,&nbsp;Mingyue Zeng,&nbsp;Youfang Chen,&nbsp;Zhesheng Wen","doi":"10.1016/j.lungcan.2025.108839","DOIUrl":"10.1016/j.lungcan.2025.108839","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to evaluate the prognostic value of quantitative N1 nodal burden metrics—including positive node count, positive station count, lymph node ratio (LNR), and lymph node station ratio (LNsR)—in patients with non-skip pN2 non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>This retrospective study included 477 non-skip pN2 NSCLC patients who underwent complete surgical resection at our center from December 2008 to December 2020. N1 metrics were dichotomized based on optimal cutoffs determined by overall survival (OS). Kaplan-Meier analysis and Cox regression models were utilized to assess disease-free survival (DFS) and OS and to identify independent prognostic factors.</div></div><div><h3>Results</h3><div>In multivariable analysis, a high N1 LNR emerged as the sole N1 metric that independently predicted worse DFS (HR = 1.47, 95 % CI: 1.05–2.04, p = 0.023). In contrast, its prognostic significance for OS was attenuated (p = 0.162). However, an advanced pT4 stage (p = 0.044) was an independent predictor of worse OS, while adjuvant therapy (p = 0.016) was associated with improved OS. Notably, subgroup analysis revealed that an elevated N1 LNR independently predicted worse DFS in the pN2a subgroup (p = 0.009). Building on this, we developed a novel three-tiered stratification (pN2a-low LNR, pN2a-high LNR, and pN2b) that effectively discriminated patient outcomes for both DFS (p &lt; 0.001) and OS (p &lt; 0.01).</div></div><div><h3>Conclusions</h3><div>N1 LNR is a powerful and independent predictor of disease recurrence in non-skip pN2 NSCLC, outperforming other N1 metrics for predicting DFS. Incorporating N1 LNR into clinical assessments, particularly for pN2a patients, can enhance prognostic accuracy and potentially guide<!--> <!-->more personalized surveillance and treatment strategies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108839"},"PeriodicalIF":4.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Threshold of adequate resection margin for sub-lobar resection in peripheral clinical stage IA1-2 non-small cell lung cancer with tumor spread through air spaces","authors":"Hanbo Pan ,&nbsp;Hui Yin ,&nbsp;Wanyu Li ,&nbsp;Weicheng Kong ,&nbsp;Jiaqi Zhang ,&nbsp;Hang Chen ,&nbsp;Zhen Ge ,&nbsp;Yu Tian ,&nbsp;Junwei Ning ,&nbsp;Zhizhuo Dai ,&nbsp;Weiyang Huang ,&nbsp;Liang Fang ,&nbsp;Min Zheng ,&nbsp;Guomo Ruan ,&nbsp;Zhongjie Chen ,&nbsp;Ming Zhang ,&nbsp;Xiaomin Niu ,&nbsp;Jia Huang ,&nbsp;Chengwei Zhou ,&nbsp;Guodong Xu ,&nbsp;Qingquan Luo","doi":"10.1016/j.lungcan.2025.108838","DOIUrl":"10.1016/j.lungcan.2025.108838","url":null,"abstract":"<div><h3>Objectives</h3><div>Sub-lobar resection (SR) is an established treatment for peripheral clinical stage IA1-2 (cIA1-2) non-small cell lung cancer (NSCLC). However, it may fail to achieve complete resection and is associated with worse survival than lobar resection (LR) in spread through air spaces (STAS)⁺ populations. This study aims to define the threshold of an adequate SR margin that may yield survival outcomes comparable to LR in peripheral cIA1-2 STAS⁺ NSCLC.</div></div><div><h3>Methods</h3><div>Consecutive patients with peripheral cIA1-2 (consolidation-to-tumor ratio &gt; 0.5) NSCLC who underwent surgery between 2010 and 2020 across seven high-volume institutions were retrospectively reviewed. Stabilized inverse probability of treatment weighting (IPTW) was applied to mitigate selection bias. The primary endpoint was overall survival (OS), and the secondary endpoint was recurrence-free survival (RFS).</div></div><div><h3>Results</h3><div>A total of 6,027 STAS⁺ and 15,994 STAS⁻ patients were included. IPTW analyses demonstrated that SR was associated with improved long-term outcomes in STAS⁻ populations, whereas LR provided superior outcomes in STAS⁺ populations. Greater resection margin length and higher margin-to-tumor ratio (MTR) were independently associated with improved OS and RFS in STAS⁺ but not in STAS⁻ patients undergoing SR. Among STAS⁺ patients undergoing SR, cut-point analysis identified threshold values of 2.5 cm for resection margin length and 1.7 for MTR, which were validated in an external multi-center cohort. These cutoff values remained effective in patients with pathological visceral pleural invasion, lymphovascular invasion, or nodal involvement, and in those undergoing either segmentectomy or wedge resection.</div></div><div><h3>Conclusions</h3><div>In peripheral cIA1-2 NSCLC, STAS status may modify the prognostic impact of both resection extent and margin. For STAS⁺ patients, an SR margin length of ≥2.5 cm or an MTR of ≥1.7 may be recommended to achieve oncologic outcomes comparable to LR.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108838"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: On the clinical irrelevance of SUCRA rankings in relapsed small-cell lung cancer","authors":"Arif Hakan Önder","doi":"10.1016/j.lungcan.2025.108837","DOIUrl":"10.1016/j.lungcan.2025.108837","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108837"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NHWD-870 suppresses tumor proliferation via the BRD4/STRADA/CCND1 axis in small cell lung cancer","authors":"Linrui Ma ,&nbsp;Xiangyu Zhang ,&nbsp;Shidong Xu ,&nbsp;Jiacheng Dai ,&nbsp;Zhe Huang ,&nbsp;Zhaohui Ruan ,&nbsp;Yuda Zhang ,&nbsp;Xuexue Zhou ,&nbsp;Yuanze Sun ,&nbsp;Yahui Chen ,&nbsp;Huan Yan ,&nbsp;Chun Zou ,&nbsp;Si Qi Xiang ,&nbsp;Jingyi Li ,&nbsp;Yangqian Chen ,&nbsp;Tian Xu ,&nbsp;Renzhi Zhang ,&nbsp;Dan Yang ,&nbsp;Fang Tian ,&nbsp;Nachuan Zou ,&nbsp;Yongchang Zhang","doi":"10.1016/j.lungcan.2025.108841","DOIUrl":"10.1016/j.lungcan.2025.108841","url":null,"abstract":"<div><h3>Background</h3><div>Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. The lack of effective targeted therapies for SCLC is a major limitation of this field. Bromodomain and Extra-Terminal (BET) inhibitors have emerged as a promising class of anticancer agents. This study aimed to evaluate the preclinical efficacy and mechanism of action of NHWD-870, a novel BET inhibitor targeting BRD4, in SCLC.</div></div><div><h3>Method</h3><div>The therapeutic effects of NHWD-870 on SCLC have been validated through compassionate use. The anti-tumor effects of NHWD-870 were explored using in vitro and in vivo models. CCK-8 assays and flow cytometry were utilized to examine cell viability, apoptosis, and mechanisms of cell cycle arrest. The in vivo effectiveness of NHWD-870 was evaluated using cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of SCLC. Mechanistic studies involving RNA sequencing, Western blotting, qPCR, and transfection were conducted to investigate and confirm the underlying mechanisms of NHWD-870.</div></div><div><h3>Result</h3><div>Our study observed the efficacy of NHWD-870 in a patient with SCLC. NHWD-870 demonstrated robust anti-tumor activity against SCLC in both in vitro and in vivo models, effectively halting tumor growth, inducing apoptosis, and disrupting the cell cycle. RNA sequencing confirmed that the cell cycle is its primary pathway of action, with BRD4, STRADA, and CCND1 identified as key targets.</div></div><div><h3>Conclusion</h3><div>NHWD-870 exhibits anti-tumor activity both in vitro and in vivo against SCLC, primarily by regulating the BRD4/STRADA/CCND1 axis and inhibiting the transition of the cell cycle from the G1 phase to the S phase. These findings highlight the therapeutic potential of NHWD-870 as a novel BET inhibitor for SCLC treatment and provide a molecular basis for further clinical development.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108841"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}