Translational lung cancer research最新文献

{"title":"Targeted dual-responsive nanocapsules for synergistic cisplatin and paclitaxel prodrug delivery in the treatment of lung cancer.","authors":"Xinyu Wang, Dan Qin, Chunyu Yao, Xiang Ji, Chuankui Li, Tao Tao, Xinyu Chen, Qicai Li, Yifan Yang, Lixiang Li, Zuyi Wang, Xiaonan Zhang, Guowen Wang","doi":"10.21037/tlcr-2026-0967","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0967","url":null,"abstract":"<p><strong>Background: </strong>The clinical application of traditional chemotherapy for treating patients with lung cancer is restricted by its poor targeting efficacy and severe systemic toxicity. In this study, we developed an acid-sensitive lipid-polymer nanocapsule (PTX/Pt@RGD) for the co-delivery of a redox-sensitive paclitaxel (PTX) prodrug and cisplatin (Pt), which can facilitate both tumor microenvironment-responsive drug release and active targeting.</p><p><strong>Methods: </strong>The physicochemical properties of the nanocapsules were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The drug-loading efficiency and release profile were analyzed via high-performance liquid chromatography (HPLC). <i>In vitro</i> antitumor activity was evaluated with Cell Counting Kit-8 assay, Annexin V/propidium iodide (PI) double staining, and Transwell assay. The underlying mechanisms were explored via reactive oxygen species (ROS) detection to assess oxidative stress levels, JC-1 mitochondrial membrane potential assay to evaluate mitochondrial dysfunction, γ-H2AX immunofluorescence to quantify DNA double-strand breaks, and Western blot analysis to determine the expression of apoptosis-related proteins. Tumor-bearing mouse models were established to assess the <i>in vivo</i> targeting efficacy, therapeutic effect, and biosafety of PTX/Pt@RGD.</p><p><strong>Results: </strong>PTX/Pt@RGD exhibited a regular spherical morphology with a particle size of 99.4 nm, a drug-loading efficiency of 2.60%, an encapsulation efficiency (EE) of 44.68%, and the ability for pH/redox dual-responsive drug release. <i>In vitro</i>, PTX/Pt@RGD induced apoptosis by promoting ROS generation, reducing mitochondrial membrane potential, causing DNA damage, and activating apoptotic proteins, resulting in a total apoptosis rate of 84.2% in the group treated with PTX/Pt@RGD. <i>In vivo</i>, arginine-glycine-aspartic acid (RGD) modification enhanced tumor-specific accumulation, effectively suppressing tumor growth and angiogenesis, and demonstrated a favorable safety profile.</p><p><strong>Conclusions: </strong>PTX/Pt@RGD integrates active targeting with pH/redox dual-responsive release, achieving a high tumor-to-background ratio and efficacy comparable to that of the free PTX/cisplatin combination, together with reduced systemic toxicity and a favorable <i>in vivo</i> safety profile. Although the <i>in vivo</i> therapeutic benefit of RGD-mediated targeting warrants further investigation, our findings support the proactive evaluation of this combinatorial nanoplatform for lung cancer combination chemotherapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"286"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant alectinib versus crizotinib in completely resected <i>ALK</i>-positive non-small-cell lung cancer: a real-world retrospective cohort study.","authors":"Yitao Yang, Shenhua Liang, Ruihe Liu, Jiayuan Tian, Xingyu Luo, Guowei Ma","doi":"10.21037/tlcr-2026-0766","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0766","url":null,"abstract":"<p><strong>Background: </strong>Following the phase III ALINA trial, adjuvant alectinib has become an important option for completely resected anaplastic lymphoma kinase (<i>ALK</i>)-positive non-small-cell lung cancer (NSCLC). However, the adjuvant role of crizotinib remains uncertain, and real-world data directly comparing adjuvant alectinib with crizotinib are limited. We compared their efficacy, central nervous system (CNS) control, and safety in this setting.</p><p><strong>Methods: </strong>This single-center retrospective cohort study included 48 patients with R0-resected stage IA-IIIB <i>ALK</i>-positive NSCLC who underwent surgery between April 2012 and October 2023. Patients received alectinib 600 mg twice daily (n=26) or crizotinib 250 mg twice daily (n=22) after surgery. The primary endpoint was the 3-year disease-free survival (DFS) rate. Survival outcomes were estimated using the Kaplan-Meier method, and unadjusted hazard ratios (HRs) were calculated using Cox regression. Safety was evaluated by treatment-related adverse events.</p><p><strong>Results: </strong>At a median follow-up of 84.6 months, alectinib was associated with longer DFS than crizotinib, with median DFS not reached versus 28.23 months, a 3-year DFS rate of 91.4% versus 41.4%, and an unadjusted HR of 0.20 [95% confidence interval (CI): 0.08-0.47]. Brain metastasis-free survival (BMFS) also favored alectinib, with 3-year BMFS rates of 95.2% versus 74.8% and an HR of 0.16 (95% CI: 0.05-0.56). Most adverse events were grade 1-2; no grade ≥3 adverse events occurred with alectinib, compared with 27.3% with crizotinib.</p><p><strong>Conclusions: </strong>In this real-world cohort of patients with completely resected <i>ALK</i>-positive NSCLC, adjuvant alectinib was associated with longer DFS, improved BMFS, and a more favorable safety profile than crizotinib. These findings are broadly consistent with the benefit of adjuvant alectinib observed in the phase III ALINA trial and support alectinib as the preferred adjuvant ALK-tyrosine kinase inhibitor (TKI) option over crizotinib. Further validation in larger multicenter real-world or prospective studies is warranted.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"269"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vietnamese expert consensus on the diagnosis and multidisciplinary management of resectable non-small cell lung cancer.","authors":"Que Kim Do, Dung Xuan Pham, Hoa Thi Thai Nguyen, Nguyen Hoang Binh, Khoi Tuan Nguyen, Trung Quoc Lam, Thiet Thanh Truong, Dung Tuan Trinh, Dung Thanh Le, Anh Tuan Le, Ha Thu Le, Dung Thi Ngoc Nguyen","doi":"10.21037/tlcr-2026-0852","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0852","url":null,"abstract":"<p><strong>Background: </strong>The management of resectable non-small cell lung cancer (NSCLC) has evolved rapidly from a surgery-centered approach toward biomarker-informed, multimodality care integrating staging, pathology, surgery, perioperative systemic treatment, and postoperative surveillance. In Vietnam, implementation remains heterogeneous across institutions, particularly in access to fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), invasive mediastinal staging, molecular testing, perioperative therapy, pathology standardization, and multidisciplinary review. This project aimed to develop a Vietnamese multidisciplinary expert consensus to contextualize contemporary international evidence for clinical practice in Vietnam.</p><p><strong>Methods: </strong>A structured, modified Delphi-informed consensus process was conducted in Vietnam between August 2025 and January 2026. The workflow comprised seven stages: scoping; a baseline practice survey; initial draft development; expert review of parts 1 and 2; post-meeting written feedback, revision, electronic recirculation, and formal voting for these sections; a multidisciplinary consensus meeting and formal voting for parts 3 and 4; and editorial harmonization and consolidation. The panel included specialists in thoracic surgery, medical oncology, respiratory medicine, pathology, nuclear medicine, radiation oncology, and related disciplines. Classes of recommendation were adapted from the European Society of Cardiology framework. All statements submitted to formal consensus voting were formally rated, with consensus predefined as at least 75% agreement.</p><p><strong>Results: </strong>The final document comprised 35 consensus statements across four domains: preoperative diagnosis and staging (n=7), surgery and postoperative surveillance (n=8), neoadjuvant and perioperative treatment (n=12), and adjuvant treatment (n=8). Across the meeting rosters, 32 unique experts were identified, with strong representation from thoracic surgery and medical oncology. The baseline survey and expert discussions highlighted implementation gaps in FDG-PET/CT, invasive mediastinal staging, biomarker testing, perioperative therapy, pathology standardization, and multidisciplinary review. All 35 consensus statements met the predefined threshold, with agreement ranging from 82% to 100%.</p><p><strong>Conclusions: </strong>These consensus statements provide a multidisciplinary, evidence-informed framework for the diagnosis and management of resectable NSCLC across the perioperative pathway. By contextualizing international evidence within Vietnamese clinical practice, the document may help improve consistency of care, support biomarker-guided and multimodality treatment, and strengthen multidisciplinary decision-making across institutions.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"289"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extremely rare primary tracheal hyalinizing clear cell carcinoma: two case reports.","authors":"Dixuan Zhang, Chudong Wang, Yuxuan Li, YenZhir Tay, Shuben Li","doi":"10.21037/tlcr-2026-0844","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0844","url":null,"abstract":"<p><strong>Background: </strong>Primary tracheal hyalinizing clear cell carcinoma (HCCC) is an exceptionally rare, low-grade malignant epithelial tumor. Its nonspecific respiratory manifestations and overlapping histopathological features with other clear cell neoplasms can delay diagnosis. Molecular alterations involving the Ewing sarcoma breakpoint region 1 (<i>EWSR1</i>) gene are diagnostically valuable; however, the clinicopathological features, optimal management, and long-term outcomes of tracheal HCCC remain insufficiently characterized. We present two cases to expand the limited evidence regarding its diagnosis and surgical treatment.</p><p><strong>Case description: </strong>Two women presented with respiratory symptoms caused by primary tracheal tumors. The first patient underwent segmental tracheal resection with end-to-end reconstruction. Histopathological and immunohistochemical findings supported HCCC, and molecular testing identified an <i>EWSR1::ATF1</i> fusion. The second patient also underwent segmental tracheal resection and reconstruction. Histopathological examination revealed tumor cells with clear cytoplasm arranged in nests and cords within a hyalinized stroma, and fluorescence in situ hybridization demonstrated <i>EWSR1</i> rearrangement, confirming the diagnosis of HCCC. R0 resection was achieved in both patients. Postoperative recovery was satisfactory, and no recurrence or metastasis was identified during the available follow-up.</p><p><strong>Conclusions: </strong>Primary tracheal HCCC should be considered in the differential diagnosis of tracheal clear cell tumors. Accurate diagnosis requires integration of histomorphology, immunohistochemistry, and molecular testing for <i>EWSR1</i> alterations. Complete surgical resection with negative margins appears to be an effective treatment for localized disease. Because late recurrence or metastasis may occur and evidence remains limited, prolonged postoperative surveillance and further accumulation of molecularly confirmed cases are warranted.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"290"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of third-generation <i>EGFR</i>-TKI rechallenge therapy in advanced non-small cell lung cancer patients with <i>EGFR</i> mutation: a retrospective cohort study.","authors":"Jiajie Sun, Xinjing Li, Bingxue Wang, Zhangxuan Chen, Yang Yao, Ranpu Wu, Xiaohua Pan, Xuanhao Xu, Yunxiao Si, Hongbing Liu","doi":"10.21037/tlcr-2026-0596","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0596","url":null,"abstract":"<p><strong>Background: </strong>Third-generation epidermal growth factor receptor (<i>EGFR</i>) tyrosine kinase inhibitors (TKIs) have become the standard treatment for <i>EGFR</i>-mutant non-small cell lung cancer (NSCLC), but acquired resistance remains inevitable. Current post-progression salvage regimens offer only modest clinical benefits, leaving an unmet need for effective late-line treatment strategies. This study evaluated the efficacy and safety of third-generation <i>EGFR</i>-TKI rechallenge as a potential salvage option for heavily pretreated resistant NSCLC patients.</p><p><strong>Methods: </strong>We retrospectively analyzed 29 patients with advanced <i>EGFR</i>-mutant NSCLC who received third-generation <i>EGFR</i>-TKI rechallenge after progression on prior third-generation <i>EGFR</i>-TKI therapy between December 2019 and August 2025. All patients had pathologically confirmed <i>EGFR</i>-mutant lung adenocarcinoma and received multi-line subsequent treatment after third-generation <i>EGFR</i>-TKIs resistance. Baseline clinical data were extracted from electronic medical records, and follow-up chest CT evaluations were conducted every 6 to 8 weeks. Outcomes were standardized using RECIST version 1.1 for tumor responses and CTCAE version 5.0 for adverse events. Survival outcomes [progression-free survival (PFS), overall survival (OS)] were analyzed via Kaplan-Meier curves and log-rank tests. The primary endpoint was PFS. Secondary endpoints included OS and disease control rate (DCR).</p><p><strong>Results: </strong>The median number of prior systemic treatment lines was 5 (range, 3-12). Third-generation <i>EGFR</i>-TKI rechallenge achieved a median progression-free survival (mPFS) of 6.0 months, a median overall survival (mOS) of 12.0 months. The DCR was 6/29 (20.7%). Treatment-related adverse events (TRAEs) occurred in 8/29 (27.6%) patients, with severe (grade ≥3) events in 3/29 (10.3%). Poorer baseline ECOG PS (3-4) was significantly associated with inferior PFS (median: 5.0 <i>vs.</i> 7.0 months, P=0.04) and OS (median: 10.0 <i>vs.</i> 25.0 months, P=0.005). Chemotherapy-containing interval therapy was associated with improved PFS (7.5 <i>vs.</i> 2.0 months, P=0.02).</p><p><strong>Conclusions: </strong>Third-generation EGFR-TKI rechallenge may provide a feasible and well-tolerated salvage option for selected heavily pretreated patients with <i>EGFR</i>-mutant NSCLC. ECOG PS and prior treatment patterns may assist in patient selection for rechallenge therapy. However, these findings are strictly exploratory and require validation in larger, controlled prospective studies.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"278"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained remission of NELL-1-positive membranous nephropathy after lung adenocarcinoma resection and during subsequent atezolizumab therapy in a 68-year-old man: a case report.","authors":"Masafumi Ikezawa, Yasuyuki Ikezawa, Mina Eguchi, Fumihiko Hattanda, Akihiro Yokoyama, Tetsuaki Shoji, Makoto Araki, Mitsuru Yanai, Yayoi Ogawa, Jun Sakakibara-Konishi, Satoshi Konno","doi":"10.21037/tlcr-2026-0756","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0756","url":null,"abstract":"<p><strong>Background: </strong>Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and may occur secondary to malignancy, with lung cancer representing one of the most frequently associated malignancies. Neural epidermal growth factor-like 1 (NELL-1), identified as a target antigen in MN in 2019, has been associated with malignancy, although reported frequencies vary across cohorts. Clinical data regarding the course of NELL-1-positive MN during cancer recurrence and immune checkpoint inhibitors (ICIs) therapy remain limited.</p><p><strong>Case description: </strong>A 68-year-old man with no significant past medical history, a 33-pack-year smoking history, and previous occupational concrete dust exposure presented with bilateral lower extremity edema. Laboratory testing revealed nephrotic syndrome [serum albumin: 1.3 g/dL, urine protein-to-creatinine ratio (UPCR): 8.0 g/gCr, serum creatinine: 1.12 mg/dL]. Renal biopsy showed diffuse glomerular basement membrane (GBM) thickening with holes, subepithelial electron-dense deposits, relative immunoglobulin G (IgG) 1 predominance, and strong NELL-1 positivity, establishing NELL-1-positive MN. Subsequent malignancy screening identified a 15-mm pulmonary nodule, which was histopathologically diagnosed as stage IIIA (pT1bN2M0) lung adenocarcinoma following surgical resection. Without corticosteroids or immunosuppressive therapy, proteinuria declined after resection; at 4 months, serum albumin was 2.4 g/dL, UPCR 2.3 g/gCr, and serum creatinine 1.1 mg/dL. Renal parameters subsequently continued to improve, without nephrotic relapse. Eight months after surgery, multiple pulmonary metastases developed, and carboplatin, nab-paclitaxel, and atezolizumab were initiated. Before ICI initiation, renal remission had been established, with serum albumin of 3.6-3.8 g/dL, serum creatinine of approximately 1.1 mg/dL, and negative proteinuria. This remission was maintained throughout approximately 15 months of atezolizumab therapy, with persistently negative proteinuria, stable renal function, a sustained partial tumor response, and no nephrotic relapse. Immunohistochemical staining of the resected primary lung tumor showed no NELL-1 expression.</p><p><strong>Conclusions: </strong>Resolution of nephrotic syndrome following tumor resection suggests a possible paraneoplastic relationship in this case of NELL-1-positive MN, despite absent NELL-1 expression in the primary tumor. Sustained renal remission during cancer recurrence and atezolizumab therapy suggests that ICI therapy may be feasible in selected patients with resolved paraneoplastic MN under close renal monitoring. This case highlights the importance of malignancy screening in patients with NELL-1-positive MN.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"291"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electromagnetic navigation bronchoscopy-guided three-dimensional conformal microwave ablation for unresectable peripheral high-risk pulmonary nodules: a mid-term assessment with no real-time intraoperative CT/cone-beam computed tomography guidance.","authors":"Yawei Liu, Yan Huang, Xiaodan Lin, Yi Rong, Liurong Mao, Shijie Lu, Junying Chen, Jiyang Chen, Xiuying Xie, Kongjia Luo","doi":"10.21037/tlcr-2026-0545","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0545","url":null,"abstract":"<p><strong>Background: </strong>Radical resection is the gold standard for high-risk pulmonary nodules; however, many patients are not candidates for surgery or who decline surgery. Electromagnetic navigation bronchoscopy-guided three-dimensional conformal microwave ablation (ENB-DCMA) is a promising minimally invasive option. This study aimed to assess the mid-term safety and efficacy of a novel ENB-DCMA strategy which employs three-dimensional conformal planning to offset respiratory-induced lesion displacement.</p><p><strong>Methods: </strong>In this single-center retrospective study, we enrolled consecutive patients with peripheral high-risk pulmonary nodules who received ENB-DCMA owing to unsuitability for or refusal to surgery and radiotherapy between March 2021 and August 2023. The three-dimensional conformal strategy enlarged the ablative margin to compensate for respiratory-induced target motion exploratively, in the absence of real-time intraoperative computed tomography/cone-beam computed tomography (CT/CBCT) guidance. The primary efficacy endpoint was local progression-free survival (LPFS) post-ablation. Safety was evaluated according to the incidence of adverse events.</p><p><strong>Results: </strong>In total, 50 patients with 62 eligible pulmonary nodules were included, with 65 ablation procedures performed in total, including repeated ablation for three lesions. The technical success rate of this procedure was 95.2%. No procedure-related mortality was observed. The median follow-up was 37.1 (range, 14.7-59.9) months. The overall 3-year LPFS rate was 82.3%, and this rate reached 95.8% among patients with sub-solid nodules. The overall incidence of adverse events was 18.0% (9/50), including 12.0% (6/50) pneumothorax, 2.0% (1/50) postoperative fever, and 4.0% (2/50) self-limiting pulmonary hemorrhage; the rate of events requiring intervention was 4.0% (2/50).</p><p><strong>Conclusions: </strong>ENB-DCMA serves as a safe and feasible minimally invasive therapeutic option for patients with high-risk pulmonary nodules. Further multicenter prospective trials are required to verify its long-term outcomes and broader clinical popularization value.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"274"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toripalimab combined with chemotherapy in the treatment of primary tracheal squamous cell carcinoma: a phase II proof-of-concept study.","authors":"Jie Dai, Xinyun Fang, Xinsheng Zhu, Xinnan Xu, Dongliang Bian, Xiaogang Liu, Wenxin He, Liang Duan, Peng Zhang, Gening Jiang","doi":"10.21037/tlcr-2026-0773","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0773","url":null,"abstract":"<p><strong>Background: </strong>Despite immunotherapy advancements for many solid cancers, role of first-line immunotherapy for tracheal malignancies is uncertain. This study aimed to evaluate the efficacy and safety of toripalimab with chemotherapy for initially-unresectable locally-advanced tracheal squamous cell carcinoma (SCC).</p><p><strong>Methods: </strong>Six eligible patients (5 males and 1 female) with tracheal SCC who were initially considered unresectable were enrolled from February 2021 to April 2023. Patients received toripalimab (240 mg) and platinum-based chemotherapy for 4 cycles. After 2 cycles of treatment, tumor was revaluated to decide further treatment, including either tracheal resection or continued immunochemotherapy and consolidation radiotherapy.</p><p><strong>Results: </strong>The median length of tumor along the trachea was 48.8 (42.5-53.3) mm. Three patients were staged as T4 and 4 patients had N1 diseases. Treatment-related adverse events (TRAEs) occurred in all patients, most were grade 1, including fatigue (100%), leukopenia (16.7%), hypokalemia (16.7%), and pruritus (16.7%), without serious TRAEs. Clinical down-staging was observed in all 6 patients, with a radiologic complete response rate of 33.3%. Two (33.3%) patients received operation: 1 had pathologic complete response and remained disease-free over 22 months postoperatively, while the other patient had R1 resection and died due to tumor relapse 10 months after diagnosis. The remaining 4 non-surgical patients remained progression-free after a median follow-up of 38.0 months.</p><p><strong>Conclusions: </strong>First-line toripalimab with chemotherapy for locally-advanced tracheal SCC showed a potential efficacy with a tolerable safety profile. Surgical conversion was possible, and further studies are needed to verify these findings, particularly in the neoadjuvant setting.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"270"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity and specificity of KRAS variants-directed Revolution Medicines Company (RMC) compounds for pleural effusion-derived non-small cell lung cancer cell lines.","authors":"Sandra Stickler, Marie-Therese Eggerstorfer, Maximilian Rieche, Lukas Weigl, Martin Hohenegger, Karl Kashofer, Maximilian J Hochmair, Gerhard Hamilton","doi":"10.21037/tlcr-2026-0798","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0798","url":null,"abstract":"<p><strong>Background: </strong>The clinical therapy for KRAS G12C mutated lung cancers has been revolutionized by the approval of the covalent inhibitors Sotorasib and Adagrasib. However, the restriction to KRAS G12C, the response rates of approximately 45% and the duration of response (DOR) of approximately 1 year leaves room for improvements. A completely new approach uses intracellular glues to block KRAS variants by steric hindrance through binding of cyclophilin A (CYPA) to the switch regions of KRAS. A series of Revolution Medicines Company (RMC) compounds were developed, targeting all KRAS variants and KRAS wildtype, namely (RMC-6236, daraxonrasib), KRAS G12C (RMC-6291, elironrasib), KRAS G12D (RMC-9805, zoldonrasib) and KRAS G12V (RMC-5217) with more agents under development. This study aimed to reveal the specificity of RMC compounds and to discover underlying resistance mechanisms in real-world tumor cell lines.</p><p><strong>Methods: </strong>Four RMC compounds were tested against a panel of 22 tumor cell lines, including 15 non-small cell lung cancer (NSCLC) lines carrying a range of KRAS mutations that were recently established from pleural effusions of lung cancer patients. Compounds were used in cytotoxicity tests and Western blot arrays comprising oncology-related proteins as well as for KRAS Western blots.</p><p><strong>Results: </strong>The RMC compounds were highly active against the wild-type KRAS cell lines but showed limited activity against the KRAS variant cell lines with approximately 50% of the NSCLC lines surviving even at the highest concentration of 2 µM with. The distinct RMC compounds targeting KRAS G12C, G12D and G12V exhibited poor selectivity for the respective NSCLC cell lines, although phosphoproteome analysis showed a uniform downregulation of the phosphorylation of ERK1/2. Cells exposed to RMC-6236 exhibited increased resistance to this drug and Western blots of KRAS revealed either increased protein expression or a shift of KRAS likely attributed to monoubiquitylation that was reported to increase KRAS activity.</p><p><strong>Conclusions: </strong>The RMC compounds directed at KRAS G12C, D and V mutations exhibit cytotoxic activity against the correspondingly mutated newly established NSCLC cell lines und suppress the MAPK pathway. However, a significant fraction of the cancer cells survives at high drug concentrations and in most cases, the compounds show a poor selectivity for the targeted variant cell lines although they partially contain specific warheads. Increased resistance to RMC-6236 has been associated with elevated expression or likely monoubiquitylation of KRAS. The limited activity of the RMC KRAS(ON) compounds may be supplemented by conventional KRAS(OFF) compounds or other glues or degraders.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"275"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of baseline hormone levels with outcomes of first-line immunotherapy in extensive-stage small cell lung cancer.","authors":"Shuxing Wang, Rui Meng, Jiheng Liu, Yang Zhao, Qian Sui, Yiyang Li, Dan Fan, Min Lu, Yue Zeng, Lu Chen, Zimeng Chen, Wenxin Li, Haohui Wang, Shijiao Yao, Aoxi Liang, Ji'an Zou, Yurong Peng, Xuecheng Liu, Zhenhua Qiu, Fang Wu","doi":"10.21037/tlcr-2026-0928","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0928","url":null,"abstract":"<p><strong>Background: </strong>Endocrine dysregulation may influence immune function and clinical outcomes in cancer. This study investigated the prognostic relevance of baseline endocrine hormones in patients with extensive-stage small cell lung cancer (ES-SCLC) receiving first-line immunotherapy.</p><p><strong>Methods: </strong>This retrospective multicenter cohort study included patients with ES-SCLC treated at multiple centers between January 2020 and December 2024. Baseline serum levels of cortisol, adrenocorticotropic hormone (ACTH), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured before treatment. Patients were stratified into high and low groups for each hormone based on median values. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis and Cox proportional hazards models.</p><p><strong>Results: </strong>A total of 377 patients were included, with a median PFS of 9.7 months and median OS of 16.7 months. Patients with high baseline cortisol had significantly shorter PFS (8.9 <i>vs.</i> 11.7 months, P=0.02) and OS (15.2 <i>vs.</i> 26.0 months, P=0.003). Elevated cortisol remained independently associated with inferior survival after multivariable adjustment [hazard ratio (HR) =1.540, 95% confidence interval (CI): 1.04-2.15, P=0.03]. In contrast, baseline ACTH, FT3, FT4, and TSH were not significantly associated with PFS or OS.</p><p><strong>Conclusions: </strong>Baseline cortisol is independently associated with survival outcomes in ES-SCLC patients receiving immunotherapy and may serve as a prognostic biomarker. These findings highlight the relevance of neuroendocrine-immune interactions and warrant prospective validation.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"268"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}