Cancer Communications最新文献

{"title":"NAT10 regulates tumor progression and immune microenvironment in pancreatic ductal adenocarcinoma via the N4-acetylated LAMB3-mediated FAK/ERK pathway.","authors":"Enhong Chen, Qin Wang, Leisheng Wang, Zebo Huang, Dongjie Yang, Changyong Zhao, Wuqiang Chen, Shuo Zhang, Shuming Xiong, Youzhao He, Yong Mao, Hao Hu","doi":"10.1002/cac2.70045","DOIUrl":"https://doi.org/10.1002/cac2.70045","url":null,"abstract":"<p><strong>Background: </strong>N-acetyltransferase 10 (NAT10) was reported to be associated with the immune microenvironment in several cancers. However, it is not known in pancreatic ductal adenocarcinoma (PDAC). This study aimed to elucidate the roles and mechanisms of NAT10 in tumor malignancy and the tumor microenvironment (TME) in PDAC.</p><p><strong>Methods: </strong>NAT10 expression and its role in tumor progression and clinical prognosis were analyzed using bioinformatics and functional assays. Downstream genes regulated by NAT10 and their underlying mechanisms were explored using acetylated RNA immunoprecipitation, quantitative polymerase chain reaction, RNA immunoprecipitation, and Western blotting. The role and mechanism of NAT10 in the PDAC TME were further explored using bioinformatics, single-cell RNA sequencing, multiplexed immunofluorescence, and flow cytometry. The association between NAT10 and immunotherapeutic response was investigated in a mouse model by inhibiting the programmed cell death 1/programmed cell death ligand 1(PD-1/PD-L1) axis with a PD-1/PD-L1 binding inhibitor, Naamidine J.</p><p><strong>Results: </strong>NAT10 was upregulated in PDAC tissues and cell lines, and was associated with poor progression-free survival of PDAC patients. NAT10 promoted tumor progression by enhancing the mRNA stability of laminin β3 (LAMB3) via N4-acetylation modification, thereby activating the focal adhesion kinase (FAK)/extracellular regulated protein kinases (ERK) pathway. NAT10 promoted subcutaneous tumor growth, increased the proportion of exhausted CD8⁺ T cells (CD8⁺ Tex), especially the intermediate CD8⁺ Tex subset, and decreased the proportion of cytotoxic CD8⁺ T cell (CD8⁺ Tc) subset in the PDAC TME. Naamidine J treatment significantly enhanced the proportion of CD8⁺ Tc subset and reduced the proportion of intermediate CD8⁺ Tex subset in mice bearing subcutaneous tumors with high NAT10 expression. Regarding the regulatory mechanism, NAT10 increased PD-L1 expression and abundance in tumor cells by activating the LAMB3/FAK/ERK pathway, thereby reducing the cytotoxicity of CD8⁺ T cells. Inhibition of the PD-1/PD-L1 axis with Naamidine J retrieved CD8⁺ T cell cytotoxicity.</p><p><strong>Conclusions: </strong>This study proposes a regulatory role of NAT10 in tumor progression and immune microenvironment via the LAMB3/FAK/ERK pathway in PDAC. These findings may favor the selection of candidates who may benefit from immunotherapy, optimize current therapeutic strategies, and improve the clinical prognosis of PDAC patients.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336319","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":"Ubiquitination in cancer: mechanisms and therapeutic opportunities.","authors":"Susi Zhu, Xu Zhang, Waner Liu, Zhe Zhou, Siyu Xiong, Jie Li, Xiang Chen, Cong Peng","doi":"10.1002/cac2.70044","DOIUrl":"https://doi.org/10.1002/cac2.70044","url":null,"abstract":"<p><p>Ubiquitination, a key post-translational modification, plays an essential role in tumor biology by regulating fundamental cellular processes, such as metabolism and cell death. Additionally, it interacts with other post-translational modifications, which are closely linked to tumorigenesis, tumor progression, the tumor microenvironment, and the response to therapeutic interventions. Recent advancements in understanding the ubiquitination mechanisms have led to significant breakthroughs, offering novel perspectives and strategies for diagnosing and treating tumors. Here, we provided an overview of how ubiquitination influences tumor biology, focusing on its roles in immune regulation, metabolism, and its interactions with other modifications. We also summarized the clinical potential of targeting E3 ubiquitin ligases and deubiquitinases as therapeutic strategies in cancer treatment.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332491","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":"Single-cell-eQTL mapping in circulating immune cells reveals genetic regulation of response-associated networks in lung cancer immunotherapy.","authors":"Hyungtai Sim, Geun-Ho Park, Woong-Yang Park, Se-Hoon Lee, Murim Choi","doi":"10.1002/cac2.70042","DOIUrl":"https://doi.org/10.1002/cac2.70042","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293362","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":"Targeting MAN1B1 potently enhances bladder cancer antitumor immunity via deglycosylation of CD47.","authors":"Jie Zhang, Chen Zhang, Ruichen Zang, Weiwu Chen, Yining Guo, Haofei Jiang, Jing Le, Kunyu Wang, Haobo Fan, Xudong Wang, Sisi Mo, Peng Gao, Wenhao Guo, Xinrong Jiang, Fengbin Gao, Junming Jiang, Juyan Zheng, Yuxing Chen, Yicheng Chen, Yanlan Yu, Guoqing Ding","doi":"10.1002/cac2.70040","DOIUrl":"https://doi.org/10.1002/cac2.70040","url":null,"abstract":"<p><strong>Background: </strong>Only a few bladder cancer patients benefit from anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy. The cluster of differentiation 47 (CD47) plays an important role in tumor immune evasion. CD47 is a highly glycosylated protein, however, the mechanisms governing CD47 glycosylation and its potential role in immunosuppression are unclear. Therefore, this study aimed to evaluate the function of CD47 glycosylation in bladder cancer.</p><p><strong>Methods: </strong>Western blotting, immunohistochemistry, and flow cytometry were used to measure protein expression, protein-protein interactions, and phagocytosis in bladder cancer. A murine model was employed to investigate the impact of mannosidase alpha class 1B member 1 (MAN1B1) modification of CD47 on anti-phagocytosis in vivo. An ex vivo model, patient-derived tumor-like cell clusters, was used to examine the effect of targeting MAN1B1 on phagocytosis.</p><p><strong>Results: </strong>Our research identified that aberrant CD47 glycosylation was responsible for its immunosuppression. The glycosyltransferase MAN1B1 responsible for CD47 glycosylation was highly expressed in bladder cancer. Abnormal activation of extracellular signal-regulated kinase (ERK) was significantly associated with MAN1B1 stability by regulating the interaction between MAN1B1 and the E3 ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1). Mechanistically, abnormally activated ERK stabilized MAN1B1, resulting in the glycosylation of CD47 and facilitating immune evasion by enhancing its interaction with signal-regulatory protein alpha (SIRP-α). In vitro and in vivo experiments demonstrated that MAN1B1 knockout weakened CD47-mediated anti-phagocytosis. MAN1B1 inhibitors promoted phagocytosis without causing anemia, offering a safe alternative to anti-CD47 therapy.</p><p><strong>Conclusions: </strong>This comprehensive analysis uncovered that ERK activation stabilizes MAN1B1 by regulating the interaction between MAN1B1 and HRD1, facilitates immune evasion via CD47 glycosylation, and presents new potential targets and strategies for cancer immunotherapy that do not cause anemia.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265308","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":"Adjuvant capecitabine in combination with docetaxel and cyclophosphamide versus anthracycline plus docetaxel and cyclophosphamide regimen in women with high-risk, HER2-negative breast cancer: An open-label, randomized controlled trial.","authors":"Yu Song, Yingjiao Wang, Xi Cao, Ying Xu, Yidong Zhou, Qiang Sun, Songjie Shen","doi":"10.1002/cac2.70041","DOIUrl":"https://doi.org/10.1002/cac2.70041","url":null,"abstract":"<p><strong>Background: </strong>The standard adjuvant chemotherapy for early-stage, high-risk breast cancer includes anthracyclines and taxanes. While anthracycline-based regimens have proven effective in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, their efficacy may be reduced in HER2-negative patients due to the lack of co-amplification of DNA topoisomerase IIα, the primary target of anthracyclines. This study compared the efficacy and safety of the regimen of docetaxel, anthracycline, and cyclophosphamide (TAC) versus a novel regimen consisting of docetaxel, cyclophosphamide, and capecitabine (TCX), hypothesizing that replacement of anthracycline with capecitabine could offer superior outcomes in this patient population.</p><p><strong>Methods: </strong>In this open-label, randomized controlled trial, 204 patients with pT1-3, node-positive or high-risk node-negative, HER2-negative early-stage breast cancer were enrolled between May 2011 and December 2013 (ClinicalTrials.gov: NCT01354522). Patients were randomized 2:1 to TAC (n = 136) or TCX (n = 68), with treatment administered every 21 days for six cycles. The primary endpoints were disease-free survival (DFS) and overall survival (OS); secondary endpoints included distant disease-free survival (DDFS), disease-specific survival (DSS), and adverse event (AE) rates.</p><p><strong>Results: </strong>With a median follow-up of 124.4 (range, 19.5-147.8) months, TCX did not significantly improve the 10-year DFS rate over TAC (71.5% ± 5.6% vs. 67.6% ± 4.0%, P = 0.477). However, the 10-year OS rate was significantly higher in the TCX group than in the TAC group (91.0% ± 3.5% vs. 77.2% ± 3.6%, P = 0.009). The TCX group also showed trends toward improved 10-year DDFS rate (82.0% ± 4.7% vs. 69.8% ± 3.9%, P = 0.052) and significantly higher 10-year DSS rate (93.9% ± 3.0% vs. 77.8% ± 3.6%, P = 0.002) compared to the TAC group. Grade 3-4 AEs occurred significantly more often in the TAC group than the TCX group (67.7% vs. 42.7%, P = 0.001).</p><p><strong>Conclusion: </strong>TCX may provide superior long-term survival and a more favorable safety profile compared to TAC for patients with high-risk HER2-negative breast cancer, warranting further investigation in larger cohorts.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257389","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":"Associations of body mass index and waist circumference with incidence of overall and of 27 site-specific cancers: a population-based retrospective cohort study.","authors":"Seonghye Kim, Bongseong Kim, Kyu-Won Jung, Ga Eun Nam, Wonyoung Jung, Junhee Park, Kyung-Do Han, Dong Wook Shin","doi":"10.1002/cac2.70039","DOIUrl":"https://doi.org/10.1002/cac2.70039","url":null,"abstract":"<p><strong>Background: </strong>Overweight and obesity are known risk factors for cancer. The aim of this study was to investigate associations of body mass index (BMI) and waist circumference (WC) with incidence of 27 site-specific cancers stratified by sex and menopausal status accounting for non-linearity.</p><p><strong>Methods: </strong>We performed a population-based retrospective cohort study using the Korean National Health Insurance Service (KNHIS 2009-2020) database. We included 3,986,155 participants (aged ≥ 20 years), and the mean follow-up duration was 9.0 ± 1.6 years. The primary outcome was the incidence of cancer.</p><p><strong>Results: </strong>There were positive associations between BMI or WC and incidences of cancers including overall cancer, digestive tract cancer (except for esophageal cancer), hepato-bilio-pancreatic cancer, hematological cancer, sex-specific cancers, brain/central nervous system (postmenopausal women), thyroid, renal, and bladder cancers. We observed inverse associations for several cancers, including lung and laryngeal cancers.</p><p><strong>Conclusions: </strong>Our findings of differential associations of BMI and WC with incidence of various cancers contribute to the understanding of the relationship between obesity and cancer risk in Asian populations. These results may provide evidence to support the implementation of active surveillance and targeted management strategies for obesity.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233284","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":"Lipid metabolism reprograming by SREBP1-PCSK9 targeting sensitizes pancreatic cancer to immunochemotherapy.","authors":"Mengyi Lao, Xiaozhen Zhang, Zejun Li, Kang Sun, Hanshen Yang, Sicheng Wang, Lihong He, Yan Chen, Hanjia Zhang, Jiatao Shi, Daqian Xu, Tingbo Liang, Xueli Bai","doi":"10.1002/cac2.70038","DOIUrl":"https://doi.org/10.1002/cac2.70038","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer's aberrant lipid metabolism fuels cell growth, invasion, and metastasis, yet its impact on immune surveillance and immunotherapy is unclear. This study investigated how sterol regulatory element-binding transcription factor 1 (SREBP1)-driven lipid metabolism affects the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Methods: </strong>Clinical significance of SREBP1 was assessed in a PDAC cohort from China and The Cancer Genome Atlas (TCGA) cohorts. The in vitro mechanisms that SREBP1 regulated programmed cell death-ligand 1 (PD-L1) and proprotein convertase subtilisin/kexin type 9 (PCSK9) were investigated using immunofluorescence, flow cytometry, Western blotting, luciferase assays and chromatin immunoprecipitation. In vivo studies using PDAC-bearing mice, humanized patient-derived tumor xenograft (PDX) models, and autochthonous model of mutation (GEMM-KTC) evaluated the efficacy and mechanisms of programmed death receptor 1 (PD-1) antibodies and lipid inhibitors.</p><p><strong>Results: </strong>Patients responding to anti-PD-1 therapy exhibited lower serum lipid levels than non-responders. Targeting SREBP1 disrupted lipid metabolism, decelerated tumor growth, and boosted the efficacy of immunotherapy for PDAC. Mechanistically, SREBP1 directly bound the PD-L1 promoter, suppressing its transcription. Meanwhile, PCSK9, a direct transcriptional target of SREBP1, modulated PD-L1 levels via lysosomal degradation. Consequently, the combination of PCSK9-neutralizing antibodies with PD-1 monotherapy showed a robust antitumor effect in both humanized PDX and GEMM-KTC models.</p><p><strong>Conclusions: </strong>The SREBP1-PCSK9 axis-mediated lipid metabolism is crucial for triggering immune evasion and resistance to anti-PD-1. Targeting the SREBP1-PCSK9 axis could potentially reverse PDAC's resistance to anti-PD-1 therapy.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172965","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":"Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma.","authors":"Jinghan Zhu, Yixiao Xiong, Yuxin Zhang, Huifang Liang, Kun Cheng, Yuanxiang Lu, Guangzhen Cai, Yang Wu, Yunhui Fan, Xiaoping Chen, Hong Zhu, Zeyang Ding, Wanguang Zhang","doi":"10.1002/cac2.70036","DOIUrl":"https://doi.org/10.1002/cac2.70036","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholangiocarcinoma (ICC) is a challenging cancer with an increasing incidence. The Phase III TOPAZ-1/KEYNOTE-966 study demonstrated chemo-immunotherapy (CIT) as a significant advancement, potentially replacing traditional chemotherapy for advanced biliary tract cancer. Ferroptosis is a crucial process that affects cancer cell survival and therapy resistance. Although AKT hyperactivation is prevalent in numerous cancers, including ICC, its role in ferroptosis resistance remains unclear. This study explored whether targeting ferroptosis can enhance CIT response rates, specifically in ICC patients with AKT hyperactivation.</p><p><strong>Methods: </strong>In vivo metabolic CRISPR screening in a Kras^G12D/Tp53^-/- ICC mouse model was used to identify primary regulators of ferroptosis during CIT (gemcitabine, cisplatin, and anti-mouse programmed cell death 1 ligand 1). Phosphoenolpyruvate carboxykinase 1 (PCK1) was assessed for its role in ferroptosis and treatment resistance in preclinical models under AKT activation levels. Molecular and biochemical techniques were used to explore PCK1-related resistance mechanisms in AKT-hyperactivated ICC.</p><p><strong>Results: </strong>Under AKT hyperactivation condition, phosphorylated PCK1 (pPCK1) promoted metabolic reprogramming, enhancing ubiquinol and menaquinone-4 synthesis through the mevalonate (MVA) pathway. This cascade was mediated by the pPCK1-pLDHA-SPRINGlac axis. Inhibiting PCK1 phosphorylation or using simvastatin significantly augmented CIT efficacy in preclinical models. Clinical data further indicated that phosphorylated AKT (pAKT)-pPCK1 levels might serve as a biomarker to predict CIT response in ICC.</p><p><strong>Conclusion: </strong>This study identified the pAKT-pPCK1-pLDHA-SPRINGlac axis as a novel mechanism driving ferroptosis resistance in AKT-hyperactivated ICC by associating glycolytic activation with MVA flux reprogramming. Targeting this axis, potentially through statin-based therapies, may offer a strategy to sensitize ICC cells to ferroptosis and improve treatment outcomes.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180794","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":"First-line serplulimab plus chemotherapy in extensive-stage small-cell lung cancer: Updated results and biomarker analysis from the ASTRUM-005 randomized clinical trial.","authors":"Ying Cheng, Shuang Zhang, Liang Han, Lin Wu, Jun Chen, Peiyan Zhao, Hongmei Sun, Guilan Wen, Yinghua Ji, Anastasia Zimina, Jianhua Shi, Zhijie Pan, Jinsheng Shi, Xicheng Wang, Yuansong Bai, Tamar Melkadze, Yueyin Pan, Xuhong Min, Maksym Viguro, Xingya Li, Yanqiu Zhao, Junquan Yang, Tamta Makharadze, Ekaterine Arkania, Haoyu Yu, Jing Li, Fang Yang, Xinyi Yang, Chen Ling, Qingyu Wang, Yongqiang Shan, Jun Zhu","doi":"10.1002/cac2.70032","DOIUrl":"https://doi.org/10.1002/cac2.70032","url":null,"abstract":"<p><strong>Background: </strong>The ASTRUM-005 study previously demonstrated a significant overall survival (OS) benefit with serplulimab (a programmed death 1 inhibitor) plus chemotherapy versus chemotherapy alone in previously untreated extensive-stage small-cell lung cancer (ES-SCLC). Here, we report updated efficacy and safety results after an extended median follow-up of 19.8 months, along with the first report on findings from exploratory biomarker analyses.</p><p><strong>Methods: </strong>A total of 585 patients were randomized in a 2:1 ratio to receive 4.5 mg/kg serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks, together with carboplatin and etoposide. The primary endpoint was OS. In addition, genomic profiling was performed to identify mutated genes, and quantitative serum proteome profiling was conducted to identify differentially expressed proteins (DEPs) between responders and non-responders of serplulimab plus chemotherapy. Regression analysis was subsequently used to construct a protein signature based on the DEPs. The associations between efficacy outcomes (objective response rate [ORR], OS, and progression-free survival [PFS]) and gene mutation status or DEP expression were also examined with regression analysis. Furthermore, the prognostic value of hematological parameters was evaluated.</p><p><strong>Results: </strong>In the intent-to-treat population, the median OS was 15.8 months in the serplulimab group versus 11.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval, 0.50-0.76; P < 0.001). We identified 181 DEPs between responders and non-responders in the serplulimab group, from which a 15-protein signature was constructed. In the serplulimab group, patients with a higher 15-protein signature score were associated with significantly longer OS and PFS. Also, patients harboring tumor-suppressor retinoblastoma-1 (RB1) mutations or mutations in Notch pathway members showed improved ORR, OS, or PFS compared with their wild-type counterparts. Baseline neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level were independent prognosticators of patients with ES-SCLC.</p><p><strong>Conclusions: </strong>First-line serplulimab provided a sustained clinical benefit over placebo in patients with ES-SCLC. A 15-protein signature and mutations in RB1 or Notch pathway genes may serve as predictive biomarkers for benefits from serplulimab plus chemotherapy, while baseline NLR and LDH were independent prognosticators for ES-SCLC.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT04063163.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180639","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":"Cell-free DNA blood-based test compared to fecal immunochemical test for colorectal cancer screening.","authors":"Teresa Seum, Michael Hoffmeister, Hermann Brenner","doi":"10.1002/cac2.70037","DOIUrl":"https://doi.org/10.1002/cac2.70037","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149246","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}