Cancer letters最新文献

{"title":"Non-Invasive Strategy for Gastric Cancer Detection: Integration of Cell-free DNA Fragmentomics and Protein Biomarkers.","authors":"Yueqing Huang, Xuefei Xu, Nannan Jiang, Wei Zhang, Haihua Shi, Qiaonan Duan, Zexin Han, Chong Zhou, Xianmin Li, Xiaoming Shen, Qinghao Tan, Shuguang Han, Fan Zheng, Ying Wang, Li Wang, Xiaoya Xu, Zhikuan Li, Sheng Chen, Dongyu Liu, Longfei Dai, Jian Wang, Dadong Zhang, Min Huang, Lian Lian, Wenjie Wang","doi":"10.1016/j.canlet.2026.218811","DOIUrl":"https://doi.org/10.1016/j.canlet.2026.218811","url":null,"abstract":"<p><p>Gastric cancer (GC) ranks as the fifth most common cancer worldwide, however, accurate and non-invasive diagnostic modalities for GC remain limited. Cell-free DNA (cfDNA) fragmentomics has emerged as a promising tool for cancer cell detection. Here we develop a gastric cancer detection model, named GaFraD model. The GaFraD model uses four cfDNA fragmentomics features, including fragment size ratio (FSR), copy number variation (CNV), 9-bp end motif (Motif), and fragment size at transcription start sites (TF). This model achieves an area under the receiver-operating characteristic curve (AUC) of 0.970 (95% CI: 0.944 - 0.990), a sensitivity of 95.0% and a specificity of 80.9%. By combining the GaFraD model and conventional protein biomarkers CA19-9 and PG-I/PG-II, the CONFIRM model was generated. The CONFIRM model attained an AUC of 0.986 (95% CI: 0.966 - 1.000), a sensitivity of 95.0% and a specificity of 95.6% in detecting GC. Moreover, the CONFIRM model achieved remarkable performance (AUC = 0.983, sensitivity 95.6%, specificity 94.2%) in distinguishing patients with early-stage GC from controls. Our work showed the high discriminatory power in distinguishing GC patients from controls, indicating the clinical potential of using cfDNA fragmentomics combined with protein biomarkers for non-invasive GC detection. The results of the study provide a new avenue for early, accurate, and non-invasive clinical diagnosis of GC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218811"},"PeriodicalIF":11.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XPO1 inhibition enhances the efficacy and durability of RAS-targeted therapy in preclinical models of KRASG12D mutant pancreatic ductal adenocarcinoma.","authors":"Husain Yar Khan, Mohammed Najeeb Al Hallak, Amro Aboukameel, Sahar F Bannoura, Md Hafiz Uddin, Adeeb A Aboukameel, Fulya Koksalar Alkan, Ahmet B Caglayan, Hilmi K Alkan, Bin Bao, Hugo Jimenez, Allan M Johansen, Callum McGrath, Grayson Barker, Khalil Choucair, Miguel Tubon, Eliza Beal, Steve Kim, Rafic Beydoun, Gregory Dyson, Yang Shi, Misako Nagasaka, Azeddine Atfi, Hasan Korkaya, Muhammad Wasif Saif, Philip A Philip, Bassel El-Rayes, Herbert Chen, Anthony F Shields, Ramzi M Mohammad, Boris C Pasche, Asfar S Azmi","doi":"10.1016/j.canlet.2026.218804","DOIUrl":"https://doi.org/10.1016/j.canlet.2026.218804","url":null,"abstract":"<p><p>KRASG12D-selective and pan-RAS inhibitors have shown promise in pancreatic ductal adenocarcinoma (PDAC), yet adaptive resistance is anticipated to limit durability of response. Exportin 1 (XPO1), a nuclear export protein frequently overexpressed in PDAC, represents a potential vulnerability in KRAS-mutant cancers. We evaluated whether pharmacologic inhibition of XPO1 enhances therapeutic efficacy and durability of KRAS pathway inhibition. KRASG12D inhibitor- and pan-RAS inhibitor-resistant PDAC cellular models were generated and assessed for sensitivity to the second-generation XPO1 inhibitor Eltanexor. Antiproliferative synergistic effects of Eltanexor combined with MRTX1133, Zoldonrasib (RMC9805), or Daraxonrasib (RMC6236) were evaluated in PDAC 2D cultures, 3D spheroids, patient-derived organoids, and tumor-fibroblast co-culture models. Eltanexor sensitized KRAS inhibitor-resistant PDAC cells and synergistically enhanced growth suppression across multiple KRASG12D-mutant models. Combination treatment reduced clonogenic survival, disrupted 3D spheroid integrity, and significantly inhibited viability of patient-derived organoids. The in vivo efficacy of the combination was tested in PDAC cell-derived xenograft/allograft and patient-derived xenograft models. Combining sub-therapeutic doses of Eltanexor with allele-specific inhibitors or pan-RASi resulted in significant tumor regression, prevention of metastatic spread and prolonged survival in vivo. Notably, Eltanexor maintenance therapy suppressed tumor regrowth following RAS inhibitor withdrawal and preserved responsiveness upon re-challenge. Mechanistically, molecular and phosphokinome profiling showed that the combination broadened suppression of MAPK- and mTOR-associated signaling and reduced activity of multiple oncogenic kinases. In conclusion, XPO1 inhibitor Eltanexor enhances the efficacy and durability of KRAS and pan-RAS inhibition in PDAC models. These findings provide a preclinical rationale for clinically evaluating Eltanexor in combination with RAS-targeted therapies to delay or overcome adaptive resistance in KRAS-mutant PDAC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218804"},"PeriodicalIF":11.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tertiary lymphoid structures in hepatocellular carcinoma: Prognostic biomarker, immunotherapy predictor, and emerging therapeutic target.","authors":"Mehriban Bazar, Ye Tian, Haijing Luan, Lin Zhang, Qian Lu, Liang Wang, Xiaojuan Wang, Jiahong Dong","doi":"10.1016/j.canlet.2026.218798","DOIUrl":"10.1016/j.canlet.2026.218798","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with many patients presenting with advanced disease that does not respond to standard treatments. While immune checkpoint inhibitors (ICIs) have improved outcomes, their effectiveness is limited in immunologically \"cold\" tumors, highlighting the urgent need to elucidate the complexity of the tumor immune microenvironment (TIME). Tertiary lymphoid structures (TLSs), ectopic and organized lymphoid aggregates that form at sites of chronic inflammation, have become key players in antitumor immunity. This review thoroughly covers the composition, multistage formation, and functional maturation of TLSs in HCC. We emphasize that the prognostic and predictive value of TLSs depends not only on their presence but also on their spatial localization, structural maturity, and specific immune cell composition. A high density of intratumoral TLSs (iTLSs), especially those with mature germinal centers containing B cells, T follicular helper (Tfh) cells, and dendritic cells (DCs), is strongly linked to better survival and lower recurrence rates. Additionally, TLSs serve as biomarkers for predicting favorable responses to ICIs in both neoadjuvant and adjuvant settings. We also explore how locoregional therapies and specific chemokine axes induce or modulate TLS formation. Finally, we discuss the emerging field of non-invasive TLS evaluation using radiomics and advanced imaging techniques, which promises to guide patient stratification for immunotherapy. TLSs therefore represent promising therapeutic targets with the potential to reprogram the immune milieu of HCC and enable more effective, personalized treatment approaches.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218798"},"PeriodicalIF":11.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Human Stem Cell Model of Neuroblastoma Identifies Four Chromosome 17q Genes that Drive Tumor Initiation and Progression.","authors":"Wanqi Fang, Bo Cheng, Steven Pastor, Michael J Zobel, Tania Porras, Hong-Wei Wu, Taneesh Kondapally, Stephen S Roberts, Chintan Parekh, Jessica W Tsai, Anestis Tsakiridis, Ivana Barbaric, Shahab Asgharzadeh, John M Maris, Miller Huang","doi":"10.1016/j.canlet.2026.218781","DOIUrl":"https://doi.org/10.1016/j.canlet.2026.218781","url":null,"abstract":"<p><p>Neuroblastoma is a pediatric solid malignancy that primarily arises from poorly differentiated sympathoadrenal cells in the developing autonomic nervous system. The neuroblastoma genetic landscape is characterized by a paucity of somatic mutations and a far more common occurrence of chromosome copy number variations (CNVs). Two of the most common genetic abnormalities in neuroblastoma are the amplification of MYCN and the unbalanced gain of the long arm of chromosome 17 (17q+), both of which correlate with poor prognosis. Although mouse models exist for MYCN-driven neuroblastoma, no mouse models exist for 17q+. Thus, the mechanism by which 17q+ contributes to poor prognosis remains largely unknown. Here, we used a human pluripotent stem cell (PSC) model of neuroblastoma to show that 17q+ cooperates with MYCN amplification to accelerate tumorigenesis compared to MYCN amplification alone. We identified six genes on 17q that are upregulated in both our 17q+ PSC-derived tumors and 17q+ neuroblastoma patient tumors compared to WT 17q, correlate with poor prognosis in neuroblastoma patients, and are overexpressed at the protein level in our MYCN/17q+ tumors compared to MYCN alone. Of these six genes, knockdown of BIRC5, CDC6, IGF2BP1, or TK1 in MYCN/17q+ cells increases tumor latency in vivo and contributes to tumor progression through diverse mechanisms. Furthermore, knockdown of CDC6, IGF2BP1, and TK1 in neuroblastoma patient-derived xenografts with 17q+ slowed growth in vivo. Our findings provide new insights into potential candidate 17q drivers of neuroblastoma tumorigenesis and possible therapeutic vulnerabilities.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218781"},"PeriodicalIF":11.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid-derived suppressor cells in the tumor microenvironment: cellular crosstalk, immunosuppressive effects, and therapeutic targets.","authors":"Lisichen Zhu, Hui Liu, Sihan Zhang, Daiming Fan, Xiaojie Yuan, Xiaoliang Gao, Yongzhan Nie","doi":"10.1016/j.canlet.2026.218803","DOIUrl":"https://doi.org/10.1016/j.canlet.2026.218803","url":null,"abstract":"<p><p>Tumor microenvironment (TME)-induced immunosuppression is a major driver of cancer treatment failure and resistance to immunotherapy. Myeloid-derived suppressor cells (MDSCs) are not only pivotal suppressors of effector immune responses but also central organizers of tumor-supportive metabolic, stromal, and cellular crosstalk. This review systematically summarizes the origin and phenotypic characteristics of MDSCs and the mechanisms governing their recruitment, expansion, and activation within the TME. This review integrates current knowledge of MDSC biology through two complementary frameworks. One framework highlights the bidirectional interactions between MDSCs and immune, tumor, stromal, endothelial, and adipocyte compartments. The other classifies therapeutic approaches according to their mechanisms and translational relevance, including combinations with immunotherapy. We further evaluate clinical translation, including lessons from unsuccessful or inconclusive trials, biomarker gaps, and rational combination strategies. Together, current evidence indicates that MDSCs represent context-dependent therapeutic nodes, while functional reprogramming, spatially resolved profiling, and patient stratification may improve immunotherapy outcomes.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218803"},"PeriodicalIF":11.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of trastuzumab deruxtecan in a new HER2+ leptomeningeal colonization model.","authors":"Dinesh Kumar, Vanesa Silvestri, Elijah F Edmondson, Imran Khan, Wei Zhang, Debbie Wei, Christina Robinson, Alexandra S Zimmer, Stanley Lipkowitz, Simone Difilippantonio, Patricia S Steeg","doi":"10.1016/j.canlet.2026.218786","DOIUrl":"10.1016/j.canlet.2026.218786","url":null,"abstract":"<p><p>Leptomeningeal metastases are devastating complications of advanced HER2+ breast cancer, with limited therapeutic options. We developed a xenograft model of human HER2+ breast cancer cell line JIMT1-BR3-LM4 leptomeningeal colonization by four iterative cycles of intrathecal injection. The model reliably produced leptomeningeal lesions in brain and spinal cord and tumor cells in the CSF, as confirmed by endpoints of BLI, MRI, pathologic analysis and immunofluorescent staining. Upon RNA-seq, the LM model exhibited significant transcriptional changes as compared to the starting brain-tropic line. In a preclinical experiment, two doses of trastuzumab deruxtecan (T-DXd) were compared to human IgG, trastuzumab (T), nab-paclitaxel (nab-P) and T + nab-P for leptomeningeal metastasis. T-DXd demonstrated efficacy in terms of BLI imaging of the brain (P < 0.0001) and spine (P = 0.008), leptomeningeal lesion number and size in the brain (P = 0.06); efficacy was dose-dependent. T-DXd 10 mg/kg reduced leptomeningeal tumor Ki67 positivity (P = 0.0008) and increased apoptosis (P < 0.0001). In the brain, a comparison of leptomeningeal and parenchymal lesion number showed a reduction by T-DXd of 53% and 72%, respectively, compared to human IgG, with comparable effects on tumor proliferation and apoptosis. T-DXd also extended median survival to 38 days compared with 20 -24 days in control IgG or T + nab-P, with some mice surviving beyond 60 days (P = 0.003). These findings support ongoing clinical translation of T-DXd for HER2+ leptomeningeal metastasis and highlight the value of this model for future therapeutic development.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218786"},"PeriodicalIF":11.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00941 Drives Chemoresistance via Modulating PKM2 Activity and Aerobic Glycolysis in Oral Squamous Cell Carcinoma.","authors":"Shule Xie, Lianxi Mai, Yu Peng, Wenhao Sun, Yupeng Wu, Yingnan Ma, Renquan Liu, Liang Qiao, Yangu Tao, Guoxin Huang, Zhaoyu Lin","doi":"10.1016/j.canlet.2026.218775","DOIUrl":"https://doi.org/10.1016/j.canlet.2026.218775","url":null,"abstract":"<p><p>Cisplatin (CDDP) resistance represents a major determinant of poor prognosis in patients with oral squamous cell carcinoma (OSCC). While long non-coding RNAs (lncRNAs) are implicated in chemoresistance pathways, their mechanistic roles in OSCC treatment failure remain incompletely defined. This study identifies LINC00941 as a CDDP resistance-associated lncRNA, with elevated expression correlating significantly with adverse OSCC prognosis. Gain- and loss-of-function assays reveal that LINC00941 overexpression promotes both aerobic glycolysis and CDDP resistance in OSCC cells. Furthermore, elevated LINC00941 expression enhances pyruvate kinase activity, thereby fostering chemoresistance in vitro and in vivo. Mechanistic investigations reveal that LINC00941 physically interacts with pyruvate kinase M2 (PKM2), enhancing its protein stability by suppressing ubiquitin-mediated proteolysis. This stabilization amplifies glycolytic flux, ultimately inducing CDDP resistance in OSCC cells. Our findings elucidate a novel lncRNA-dependent pathway governing chemoresistance and propose targeting the LINC00941/PKM2/glycolysis axis as a translatable therapeutic strategy for overcoming CDDP resistance in OSCC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218775"},"PeriodicalIF":11.8,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyploid giant cancer cells: A hidden cost of Aurora Kinase inhibitors and antimitotic therapies revealed through the PGCC Explorer.","authors":"Kok-Siong Poon","doi":"10.1016/j.canlet.2026.218742","DOIUrl":"https://doi.org/10.1016/j.canlet.2026.218742","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218742"},"PeriodicalIF":11.8,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial FOXP3: The Silent Spark That Lights the Fire of Pancreatic Cancer.","authors":"Charles J David","doi":"10.1016/j.canlet.2026.218738","DOIUrl":"https://doi.org/10.1016/j.canlet.2026.218738","url":null,"abstract":"<p><p>For decades, we have viewed pancreatic fibrosis as a passive scar-the end-stage wreckage of chronic inflammation or a late accomplice of growing tumors. A recent study by He Ren and colleagues sheds critical light on the origins of the phenomenon tracing it to an unexpected cellular culprit: a rare subset of pancreatic epithelial cells that express FOXP3-a transcription factor predominantly associated with regulatory T cells. These epithelial FOXP3 (E-FOXP3) positive cells do not need oncogenic Kras or overt inflammation to ignite fibrosis. On their own, they orchestrate a glycosylation-dependent IL-6 switch that turns quiescent pancreatic stellate cells into a self-amplifying fibrotic machine. In discovering a proto-fibrogenic \"trigger cell\" that acts silently, long before any symptom or radiological sign, the work redefines the cellular hierarchy of pancreatic fibrocarcinogenesis. Further, the paper identifies a post-translational \"sugar code\" as a therapeutic foothold, and opens a long-sought preemptive window for intercepting pancreatic cancer at its most curable stage-before the desmoplastic fortress is ever built.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218738"},"PeriodicalIF":11.8,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein kinase Cι-driven macrophage infiltration mediates immunosuppression in non-small cell lung cancer","authors":"Shichuan Hu ,&nbsp;Zichen Zhao ,&nbsp;Jing Zhao ,&nbsp;Yilin Liang ,&nbsp;Lingye Zeng ,&nbsp;Yifei Xia ,&nbsp;Haoya Guo ,&nbsp;Lili Jiang ,&nbsp;Yan Zhang","doi":"10.1016/j.canlet.2026.218330","DOIUrl":"10.1016/j.canlet.2026.218330","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains the leading cause of cancer-related mortality. Immune checkpoint inhibitors (ICIs) targeting the programmed death-1/programmed death ligand 1 (PD-1/PD-L1) axis can induce durable tumor regression in a subset of NSCLC patients; however, most exhibit resistance to ICIs therapy. Here, we identify the protein kinase Cι (PKCι)) as a biomarker and critical mediator of poor ICIs responsiveness in NSCLC. High PKCι expression correlates with resistance to anti-PD-1 antibody (αPD1) therapy, whereas low PKCι expression are highly sensitive. PKCι-dependent resistance to αPD1 is characterized by increased tumor-associated macrophages (TAMs) infiltration and reduced CD8+T cell numbers. Mechanistically, PKCι regulated Yap1-dependent transcription of CCL7, which recruits TAMs and fosters an immunosuppressive microenvironment. In contrast, Overexpression of PKCι or CCL7 in PKCι-knockdown tumors restores TAMs infiltration and αPD1 resistance. Pharmacological inhibition of PKCι with auranofin (AF) reduces TAMs accumulation and promotes CD8+T cell infiltration by inhibiting the PKCι-Yap1-CCL7 axis. Combination therapy with AF and αPD1 triggers a CD8+T cell-dependent antitumor immune response, thereby controlling tumor growth in situ or subcutaneously. In summary, our study reveals a PKCι-mediated immunosuppressive pathway driving ICIs resistance and support PKCι inhibition as a promising strategy to enhance immunotherapy efficacy in NSCLC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"644 ","pages":"Article 218330"},"PeriodicalIF":10.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}