Cancer Science最新文献

{"title":"Urinary Small Extracellular Vesicle DNA as a Biomarker for the Non-Invasive Diagnosis of Bladder Cancer","authors":"Tao Wang,&nbsp;Xin Liao,&nbsp;Jiyang Zhang,&nbsp;Xiaoya Xu,&nbsp;Wei Zhang,&nbsp;Xinlin Chen,&nbsp;Xinyu Zhai,&nbsp;Tongtong Zhang,&nbsp;Xiangyang Zhan,&nbsp;Xingyu Mu,&nbsp;Dadong Zhang,&nbsp;Jian Chen,&nbsp;Dongliang Xu,&nbsp;Mingyue Tan","doi":"10.1111/cas.70455","DOIUrl":"10.1111/cas.70455","url":null,"abstract":"<p>Existing diagnostic technologies for bladder cancer (BC) suffer from low sensitivity, low specificity, or a lack of validation. Therefore, validated, non-invasive diagnostic biomarkers with high sensitivity and specificity for early detection of BC are needed to complement and improve upon the limitations of existing diagnostic methods. We used low-pass whole genome sequencing (LP-WGS) technology to detect copy number variations (CNVs) in small extracellular vesicle (sEV) DNA isolated from urine samples of patients. Based on these results, we constructed and validated a diagnostic model to differentiate between benign and malignant bladder lesions. We conducted a receiver operating characteristic analysis and calculated the area under the curve (AUC) to evaluate the performance of the diagnostic model. The urine sEV-DNA LP-WGS data revealed CNV differences between benign and malignant samples. The diagnostic model achieved an AUC of 0.953, a sensitivity of 86.7%, and a specificity of 100% in the training cohort and an AUC of 0.985, a sensitivity of 90%, and a specificity of 100% in the validation cohort. Even at the lowest coverage depth of 0.01X, the performance of the diagnostic model remained relatively robust. Notably, the performance of this diagnostic model surpassed that of the biomarker neuron-specific enolase (sensitivity: 85.7% vs. 64.3%; specificity: 100% vs. 87.5%) and urinary cytology (sensitivity: 100% vs. 66.7%; specificity: 100% vs. 94.1%). Our study demonstrates that urine sEV-DNA exhibits high discriminatory power in distinguishing between benign and malignant bladder lesions, making it a promising tool for auxiliary diagnosis of BC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 9","pages":"2543-2554"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392141","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":"Targeting Cell Cycle Vulnerabilities in Cancers: Emerging Strategies for Therapeutic Development","authors":"Nana Kamakura,&nbsp;Minji Jo,&nbsp;Motoko Takahashi,&nbsp;Toru Hirota","doi":"10.1111/cas.70438","DOIUrl":"10.1111/cas.70438","url":null,"abstract":"<p>Cell division is a fundamental cellular process that ensures propagation of genetic material to daughter cells. This process relies on the fidelity of DNA replication and chromosome segregation and is primarily regulated by sequential activity of cyclin-dependent kinases (Cdks) in the cell cycle program. Mitogenic signals lead to the activation of Cdks and promote cell cycle progression, whereas checkpoints act as surveillance systems to halt cell cycle progression in response to abnormal conditions. In cancers, these regulatory networks are frequently disrupted due to continuous activation of mitogenic/oncogenic signaling and/or loss of checkpoint control, resulting in uncontrolled cell cycle progression and thus genome instability. Nevertheless, cancer cells often maintain robust cell cycle control by virtue of compensatory mechanisms. Counterintuitively, however, this apparent robustness increases sensitivity to perturbations and creates unique targetable vulnerabilities. Intervening in these vulnerabilities in the cell cycle control is therefore the rationale for the effective and selective cancer treatment. In this review, we summarize emerging insights into how we can interfere with cancer cell proliferation by targeting the cancer specific vulnerabilities arising from cell cycle dysregulation. We highlight advances in targeting Cdks, checkpoint kinases and mitotic kinases, as well as recent discoveries from CRISPR-genetic screens that reveal synthetic lethal genes. Understanding these vulnerabilities provides a framework for developing cancer therapies that exploit specific dependencies in cell cycle control.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 9","pages":"2335-2344"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139551","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":"KPNA2 Drives Immunosuppression in Ovarian Cancer via CCL2/CCR2-Dependent MDSC Recruitment","authors":"Qingli Li,&nbsp;Jitong Zhao,&nbsp;Lu Yang,&nbsp;Lin Li,&nbsp;Ce Bian,&nbsp;Tao Yi,&nbsp;Huiqiong Huang,&nbsp;Gang Zheng,&nbsp;Xiaojuan Lin","doi":"10.1111/cas.70440","DOIUrl":"10.1111/cas.70440","url":null,"abstract":"<p>Immunosuppression in ovarian cancer is primarily driven by myeloid-derived suppressor cells (MDSCs). This study identifies karyopherin α2 (KPNA2) as a novel regulator of this immunosuppressive process through the NF-κB/CCL2/CCR2 axis. Elevated KPNA2 expression correlates with increased intratumoral MDSC accumulation and impaired CD8⁺ T-cell function. Mechanistically, KPNA2 directly binds to and facilitates nuclear translocation of NF-κB/p65, thereby driving CCL2 transcription, while also exhibiting an auxiliary, p65-independent function in CCL2 induction. Secreted CCL2 recruits MDSCs in a CCR2-dependent manner, establishing a potent immunosuppressive tumor microenvironment. Therapeutic targeting via MDSC depletion, pharmacological CCR2 blockade, or direct KPNA2 knockdown effectively inhibited metastasis, enhanced CD8+ T-cell infiltration, and suppressed tumor growth. Importantly, CCR2 inhibition synergized with anti-PD-L1 therapy, revealing a promising combination immunotherapeutic strategy for KPNA2-high ovarian cancer. These findings establish the KPNA2-governed NF-κB/CCL2/CCR2 pathway as a central mechanism of immune evasion and a viable target for combination immunotherapy in ovarian cancer.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 9","pages":"2461-2479"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303630","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":"ADSC-Derived CCL8 Regulates HIF-1α Signaling and Promotes Colorectal Cancer Progression in a 3D Coculture Platform","authors":"Jeong-Eun Yun,&nbsp;Yeseon Son,&nbsp;Jieun Seo,&nbsp;Ki Yong Hong,&nbsp;Junji Fukuda,&nbsp;Do-Won Jeong,&nbsp;Jong-Wan Park,&nbsp;Yang-Sook Chun","doi":"10.1111/cas.70449","DOIUrl":"10.1111/cas.70449","url":null,"abstract":"<p>This study aimed to recapitulate adipose-tumor interactions within the colorectal cancer (CRC) tumor microenvironment (TME) and to elucidate the role of adipose-derived stem cells (ADSCs) in regulating CRC progression through cytokine-mediated signaling. Human ADSCs were isolated from adipose tissue and directly cocultured with CRC cells using an oxygen-permeable, PDMS-based 3D coculture chip, followed by cytokine profiling of conditioned media, immunofluorescence analysis of spheroids, FACS-based cell separation, and molecular analyzes including western blotting, qPCR, and immunoprecipitation to interrogate HIF-1–related mechanisms. The results revealed that cancer-associated ADSCs secrete CCL8, which markedly enhances CRC cell migration. Mechanistically, ADSC-derived CCL8 activated the ERK signaling pathway in CRC cells, leading to increased HIF-1α protein accumulation without significant changes in protein stability. This was accompanied by enhanced interaction between HIF-1α and the transcriptional cofactor p300. Consequently, HIF-1α transcriptional activity was increased, resulting in the upregulation of downstream epithelial–mesenchymal transition markers and promoting a pro-migratory and aggressive cancer phenotype. These effects were particularly pronounced in the coculture system, where intensified crosstalk between ADSCs and cancer cells amplifies oncogenic signaling within the TME. Collectively, these findings demonstrate that ADSC-derived CCL8 functions as a key mediator of adipose-tumor crosstalk in CRC progression by driving HIF-1α–dependent signaling pathways. Furthermore, the PDMS-based 3D coculture platform employed in this study provides a robust and physiologically relevant experimental system for dissecting complex cell–cell interactions and cytokine-driven mechanisms within the TME of CRC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 9","pages":"2480-2495"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240479","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":"Prospective Trial on Tolerability and Efficacy of Adjuvant Nedaplatin Plus Docetaxel for Non-Small Cell Lung Cancer","authors":"Koji Teramoto,&nbsp;Ryosuke Kaku,&nbsp;Tomoyuki Igarashi,&nbsp;Masayuki Hashimoto,&nbsp;Shoji Kitamura,&nbsp;Makoto Motoishi,&nbsp;Yuji Suzumura,&nbsp;Satoru Sawai,&nbsp;Yataro Daigo,&nbsp;Jun Hanaoka","doi":"10.1111/cas.70446","DOIUrl":"10.1111/cas.70446","url":null,"abstract":"<p>Nedaplatin is a second-generation platinum compound with reduced nephrotoxicity compared with cisplatin. Given its favorable tolerability in advanced non-small cell lung cancer (NSCLC), we prospectively evaluated the tolerability and efficacy of an adjuvant nedaplatin plus docetaxel chemotherapy regimen in patients with completely resected NSCLC. Patients with stage IB–IIIA NSCLC who had undergone complete surgical resection received nedaplatin (80 mg/m²) and docetaxel (60 mg/m²) intravenously on day 1 once every 4 weeks for up to four cycles. The primary endpoint was treatment tolerability, defined as completion of the planned four cycles, and compared with historical data for the standard cisplatin plus vinorelbine regimen. The secondary endpoint was efficacy, determined by relapse-free survival (RFS) after surgery. Thirty-five patients were enrolled, with median age of 65 years (range, 36–77 years). Adenocarcinoma (57.1%) and stage II disease (60.0%) were most common. Dose reductions were needed in some patients, however, 74.3% of patients (<i>n</i> = 26) completed all four cycles, meeting the primary endpoint. Grade 3 or 4 neutropenia and anorexia occurred in 67.8% and 9.0% of patients, respectively. No grade 3 or 4 renal dysfunction was noted. Concerning efficacy, the median RFS time was 63 months (95% confidence interval [CI], 20–NE), and the 5-year overall survival rate was 85.7% (95% CI, 70.0–93.9). Long-term retrospective follow-up (median: 119 months) showed that the 10-year RFS rate was 52.9% (95% CI, 36.1–69.1). These results indicate that adjuvant chemotherapy with nedaplatin plus docetaxel is tolerable and effective in patients with completely resected NSCLC.</p><p><b>Trial Registration:</b> UMIN number: 000004634</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 9","pages":"2535-2542"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240472","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":"Bile-Derived Exosomal miR-196a/-196b as Diagnostic Biomarkers Associated With Tumor Progression in Biliary Tract Cancer","authors":"Naotaka Kugiyama,&nbsp;Katsuya Nagaoka,&nbsp;Takehisa Watanabe,&nbsp;Michihiro Yoshida,&nbsp;Tadashi Toyohara,&nbsp;Cheng Pan,&nbsp;Kenyu Hashimoto,&nbsp;Fumiya Otsuka,&nbsp;Shinya Ushijima,&nbsp;Yukiko Uramoto,&nbsp;Hajime Iwasaki,&nbsp;Motohiro Yoshinari,&nbsp;Shunpei Hashigo,&nbsp;Kazuki Hayashi,&nbsp;Itaru Naitoh,&nbsp;Fumihiro Okumura,&nbsp;Hiromu Kondo,&nbsp;Kaiki Anbe,&nbsp;Hiromitsu Hayashi,&nbsp;Yoshihiro Komohara,&nbsp;Yasuhito Tanaka","doi":"10.1111/cas.70443","DOIUrl":"10.1111/cas.70443","url":null,"abstract":"<p>Bile-based liquid biopsy presents a promising approach for identifying novel biomarkers for biliary tract cancer (BTC) given its proximity to tumor sites. The aim of this study was to identify bile-derived exosomal microRNAs (miRNAs) with diagnostic potential for BTC. The candidate miRNAs were initially screened by RNA sequencing of exosomal RNA from the bile samples of 10 BTC patients and 10 controls, resulting in the identification of miR-196a, miR-196b, and miR-424. Subsequent validation using TaqMan PCR in an independent cohort (50 BTC, 53 controls) confirmed that miR-196a and miR-196b were specifically elevated in the bile of BTC patients, with miR-196a also elevated in early-stage BTC. MiR-196a achieved an area under the receiver operating characteristic curve (AUROC) of 0.79 for the diagnosis of BTC. The combination of miR-196a and CA19-9 increased the AUROC to 0.86, and further improvement to 0.88 was observed upon the addition of CEA. Furthermore, serum levels of these miRNAs were analyzed in 64 BTC patients and 79 controls; serum miR-196a levels were significantly elevated in patients with metastatic BTC. Analysis of public datasets confirmed that both miR-196a and miR-196b were significantly upregulated in invasive BTC tissues compared to normal biliary epithelium and biliary intraepithelial neoplasia. Functional assays demonstrated that miR-196a and miR-196b promoted the proliferation and invasion of cholangiocarcinoma cells (<i>p</i> &lt; 0.05). In conclusion, bile-derived exosomal miR-196a and miR-196b are novel BTC-specific biomarkers. MiR-196a may contribute to early BTC detection, enhance diagnostic accuracy in combination with serum markers, and assist in detecting metastasis.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 9","pages":"2521-2534"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206758","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":"The Natural Quassinoid Brusatol Enhances Venetoclax Efficacy and Overcomes Resistance in Myeloid Leukemias","authors":"Shin-ichiro Kawaguchi,&nbsp;Kazuya Sato,&nbsp;Junko Izawa,&nbsp;Norihito Takayama,&nbsp;Hiroko Hayakawa,&nbsp;Ken Suzaki,&nbsp;Susumu Goyama,&nbsp;Chiyoko Kato,&nbsp;Eiji Sakashita,&nbsp;Kaoru Tominaga,&nbsp;Hitoshi Endo,&nbsp;Yoshinobu Kanda","doi":"10.1111/cas.70423","DOIUrl":"10.1111/cas.70423","url":null,"abstract":"<p>While venetoclax-based combinations have shown promising results in acute myeloid leukemia (AML), the remission duration is generally short, warranting strategies to further improve efficacy and overcome resistance. Here, we show that the natural quassinoid brusatol induces cell-cycle arrest and apoptosis in multiple AML cell lines while enhancing venetoclax efficacy irrespective of inherent or acquired resistance. Mechanistically, brusatol increased p53 protein expression, leading to upregulation of its target genes/proteins, including <i>CDKN1A</i> (p21) and <i>BBC3</i> (PUMA). Genetic deletion of <i>TP53</i> attenuated brusatol-induced apoptosis and its synergy with venetoclax, supporting p53 activation as a central mechanism underlying the anti-leukemia response. Furthermore, the combination synergistically decreased mitochondrial membrane potential and respiratory activity, causing accumulation of reactive oxygen species in AML cells. Although brusatol and venetoclax exhibited limited effects individually, their combination markedly reduced leukemia burden and significantly prolonged survival in three independent cell line-derived xenograft models, including venetoclax-resistant and -refractory models. Notably, brusatol increased normal leukocyte and platelet counts while reducing leukemic infiltration in both bone marrow and extramedullary sites. These findings provide mechanistic insight into the synergistic effects of the brusatol-venetoclax combination, supporting further evaluation of this therapeutic strategy in myeloid leukemias.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 8","pages":"2274-2288"},"PeriodicalIF":4.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989212","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":"Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer","authors":"Kaibo Guo,&nbsp;Yuqian Feng,&nbsp;Jiamin Lu,&nbsp;Nuerbiye Abudurexiti,&nbsp;Xinlei Zhou,&nbsp;Mengfan Wei,&nbsp;Song Zheng","doi":"10.1111/cas.70426","DOIUrl":"10.1111/cas.70426","url":null,"abstract":"<p>Pyroptosis, a form of programmed cell death mediated by gasdermin proteins, has gained attention for its dual role in colorectal cancer (CRC) progression and therapy. While chronic pyroptosis-driven inflammation can promote tumorigenesis, acute induction of pyroptosis in tumor cells offers promising antitumor effects. Understanding the mechanisms and implications of pyroptosis in CRC could lead to novel therapeutic strategies. Gasdermin proteins, particularly GSDMD and GSDME, are central to pyroptotic processes in CRC. GSDMD activation, often through NLRP3 inflammasome signaling or chemotherapeutic agents like simvastatin, induces pyroptosis and modulates immune infiltration. Conversely, GSDMC has been implicated in CRC progression under metabolic stress by recruiting immunosuppressive cells. Although frequently silenced in CRC, GSDME enhances sensitivity to chemoradiation and synergizes with immune checkpoint inhibitors by releasing immunostimulatory molecules. Inflammasomes, notably NLRP3 and AIM2, also play significant roles in CRC pathogenesis through pyroptosis and cytokine secretion. NLRP3 activation exacerbates tumor growth via inflammatory pathways, while AIM2 exerts tumor-suppressive effects, especially in BRAF-mutant CRC. The gut microbiota further influences inflammasome activity, with certain strains promoting chemoresistance and others enhancing antitumor immunity. Therapeutically, inducing pyroptosis synergizes with conventional therapies and immunotherapies, overcoming apoptosis resistance and resensitizing tumors. Pyroptosis releases tumor antigens and damage-associated molecular patterns, recruiting cytotoxic lymphocytes and natural killer cells, thereby remodeling the immunosuppressive microenvironment. Pyroptosis represents a double-edged sword in CRC, offering both challenges and opportunities. Harnessing its antitumor potential while mitigating pro-tumorigenic inflammation requires innovative strategies. Future research should focus on elucidating the isoform-specific roles of gasdermins, optimizing therapeutic approaches to induce pyroptosis.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 8","pages":"2064-2084"},"PeriodicalIF":4.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148044292","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":"Interpreting Early-Onset Colorectal Cancer in Japan: A Descriptive Epidemiologic Review Using Public Summary Statistics","authors":"Keitaro Matsuo,&nbsp;Hidemi Ito","doi":"10.1111/cas.70428","DOIUrl":"10.1111/cas.70428","url":null,"abstract":"<p>Early-onset colorectal cancer (EOCRC) is increasingly described as a rising disease entity, but the descriptive epidemiologic conditions required to interpret that rise remain incompletely articulated. Using Japanese public summary statistics, we conducted a reproducible descriptive epidemiology review to examine whether the observed EOCRC signal is more compatible with substantial detection-related effects, a concurrent increase in invasive burden, or both. We integrated age-group-specific incidence and mortality trends and, where available, decomposed incidence into invasive disease, incidence including in situ lesions, and the in situ component. Colorectal cancer was the primary case study, and other organized screening-target cancers were used as descriptive contrasts. In Japan, EOCRC showed increasing early-onset-to-older-adult incidence ratios, but these patterns should be interpreted alongside marked in situ amplification and limited concordance with mortality. Cross-cancer contrasts further aided interpretation: Unlike CRC, stomach cancer and male lung cancer did not show a comparable early-onset upswing over the 2003–2015 comparison window, arguing against a uniform early-onset pattern across screening-target cancers. These descriptive findings are compatible with substantial detection-related effects, but they do not exclude biologic heterogeneity or a concurrent increase in invasive EOCRC. Although public summary statistics cannot establish etiology, they can clarify what current trend data do and do not support. In particular, incidence trends alone are insufficient to justify a true-rise interpretation of clinically significant early-onset colorectal cancer.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 8","pages":"2040-2049"},"PeriodicalIF":4.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057721","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":"A cDC1-NK/T-Malignant Cell Circuit Drives Immunogenic Remodeling Under PD-1 Blockade in Gastric Cancer","authors":"Takuya Nakatsuru,&nbsp;Hiroki Yamashita,&nbsp;Chiaki Mashima,&nbsp;Guoqiang Zhang,&nbsp;Hitoshi Saito,&nbsp;Tatsunori Minamide,&nbsp;Keita H. Nagaoka,&nbsp;Ryo Kamata,&nbsp;Shunsuke A. Sakai,&nbsp;Gaku Yamamoto,&nbsp;Tomoko Y. Morita,&nbsp;Kazuki Nakai,&nbsp;Yumi Hakozaki,&nbsp;Kumi Kinoshita,&nbsp;Yui Takahashi,&nbsp;Izuma Nakayama,&nbsp;Akihito Kawazoe,&nbsp;Yuko Ishii,&nbsp;Sai M. Pulukuri,&nbsp;Hiroshi Haeno,&nbsp;Yukie Kashima,&nbsp;Kohei Shitara,&nbsp;Tomonori Yano,&nbsp;Takeshi Saito,&nbsp;Akihiro Ohashi","doi":"10.1111/cas.70381","DOIUrl":"10.1111/cas.70381","url":null,"abstract":"<p>The gastric cancer (GC) tumor microenvironment (TME) constitutes a complex and dynamic ecosystem in which immune, stromal, and malignant cells (MCs) collectively shape therapeutic responses. The dynamics of GC TME remodeling in different treatment contexts remain unclear. We performed single-cell RNA sequencing (scRNA-seq) of GC biopsy specimens from treatment-naïve patients (TN) and patients treated with chemotherapy (C), chemotherapy plus nivolumab (CN), or chemotherapy plus trastuzumab (CT), and found that CN treatment enhanced natural killer (NK)/T cell-associated immunogenicity in GC TMEs. In CN TMEs, MCs upregulate MHC-I- and inflammation-related genes. Conventional type 1 dendritic cells (cDC1), one subcluster of dendritic cells (DCs), concurrently exhibited activation of antigen-presentation and T cell-stimulatory programs, indicating intensified communication between NK/CD8⁺ T cells and cDC1 in the CN TMEs. The cell–cell interaction analyses uncovered an intensified X-C Motif Chemokine Ligand 1 (XCL1) - X-C motif chemokine receptor 1 (XCR1) chemotactic axis linking NK/CD8⁺ T cells and cDC1, highlighting the formation of “the MCs-cDC1-NK/CD8⁺ T cells circuit” to reinforce antitumor immunity in the CN TMEs. Furthermore, a reduced cytotoxic NK sub-cluster, which showed high XCL1 expression, was enriched among CN responders, and its transcriptional signature was significantly correlated with favorable survival in the Cancer Genome Atlas GC cohort. Our findings delineate an immunostimulatory circuit driven by NK/CD8⁺ T-DCs–MCs interactions to orchestrate the immune cycle under CN therapy in GC TMEs.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 8","pages":"2098-2114"},"PeriodicalIF":4.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989842","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}