Cancer Science最新文献

{"title":"Targeting Inflammation and Immune Regulation in Chronic Inflammation Associated Cancers.","authors":"Lawan Rabiu, Mengzhu Chinn, Feng Chen, Yerkezhan Yerkinkazhina, Yuan Tian, Wei-Guo Zhu","doi":"10.1111/cas.70360","DOIUrl":"10.1111/cas.70360","url":null,"abstract":"<p><p>Chronic inflammation is a fundamental driver of cancer development, linking persistent immune activation to genomic instability, microenvironmental remodeling, and malignant transformation. In inflammation-associated malignancies such as colitis-associated cancer (CAC) and metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma (MAFLD-HCC), sustained inflammatory signaling integrates tissue injury with oncogenic pathways to promote tumor initiation and progression. Importantly, these cancers arise through prolonged preneoplastic stages, during which dysregulated immune and inflammatory responses not only drive malignant transformation but also create opportunities for cancer prevention and early disease interception. CAC and MAFLD-HCC share convergent mechanisms, including IL-6/STAT3 and NF-κB activation, cytokine-driven survival signaling, and cooperation with genetic alterations in APC, KRAS, and TP53. A critical but often underappreciated dimension of this process is the failure of endogenous immunoregulatory systems that normally restrain excessive inflammation. Among these, the negative regulator of immune cells TIPE2 plays an important role in limiting inflammatory signaling, and its reduced activity contributes to the persistence of a tumor-promoting inflammatory microenvironment that supports both disease initiation and progression. This review synthesizes the shared inflammatory, immunologic, and microenvironmental mechanisms underpinning CAC and MAFLD-HCC, with a particular emphasis on how impaired immune regulation drives the transition from chronic inflammation to cancer. We further highlight therapeutic and preventive strategies targeting inflammation-driven pathways, underscoring the dual relevance of immune modulation for cancer prevention in chronic inflammatory disease and for the treatment of established malignancy.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1209-1222"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436799","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":"Small Cell Lung Cancer Establishes a Metabolic Autocrine Mechanism Through Active Extracellular ATP Transport.","authors":"Takeshi Tsuruda, Manabu Kodama, Keiichi I Nakayama","doi":"10.1111/cas.70350","DOIUrl":"10.1111/cas.70350","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is an aggressive malignancy with a 5-year survival rate of less than 7%. SCLC is characterized by accelerated de novo purine nucleotide biosynthesis, which fuels its rapid proliferation. While ATP serves as an essential metabolic substrate for nucleotide polymer synthesis and as the universal energy currency that fuels essential biological processes, it can also act as a potent extracellular signaling molecule. Here, we identify an autocrine mechanism in which SCLC actively exports ATP to the extracellular space through pannexin 1 (PANX1) channels, thereby promoting its own proliferation via purinergic signaling. Marked elevation of extracellular ATP was observed in SCLC cells. Clinical meta-analysis revealed that high PANX1 expression is significantly associated with poor survival in SCLC patients. Pharmacological inhibition or genetic knockdown of PANX1 suppressed extracellular ATP levels and markedly reduced SCLC cell proliferation, whereas PANX1 overexpression increased extracellular ATP and accelerated growth. This ATP efflux is driven by calcium-dependent activation of PANX1, with the calcium/calmodulin-dependent protein kinase II (CaMKII)-TRPA1 axis identified as a key upstream regulator. Moreover, blockade of the P2RX7 receptor abrogated ATP-induced proliferation, indicating that SCLC establishes a metabolic autocrine loop through ATP release and P2RX7 activation. In mouse xenograft models, PANX1 knockdown suppressed, whereas PANX1 overexpression enhanced, tumor growth in vivo. These findings indicate that SCLC exploits a PANX1-dependent ATP release mechanism to engage P2RX7-mediated autocrine signaling and suggest that targeting this axis may represent a potential therapeutic opportunity for this lethal cancer.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1333-1345"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345539","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":"GPRC5B Identified by m5C meRIP-Seq Suppresses Apoptosis in Osteosarcoma Through NSUN2-Mediated RNA Methylation.","authors":"Zhenyi Chen, Min Yang, Xiaoxiao Liang, Zhiqiang Yang, Wulan Mai, Yuyang Wang, Yushen Lu, Ruimin Wang, Yuanhang Han, Yuanlong Xie, Lin Cai","doi":"10.1111/cas.70362","DOIUrl":"10.1111/cas.70362","url":null,"abstract":"<p><p>Osteosarcoma, the most common primary malignant bone tumor with poor prognosis, underscores the need for a deeper understanding of its molecular mechanisms. Recent studies have highlighted the importance of RNA modifications, including 5-methylcytosine (m5C), in cancer progression, yet the m5C modification landscape in osteosarcoma remains unexplored. Here, we performed transcriptome-wide profiling of m5C modifications in osteosarcoma using meRIP-seq and RNA-seq, analyzing four pairs of osteosarcoma and adjacent normal tissues. Furthermore, through conjunction analyses of meRIP-seq and RNA-seq data, we identified 637 genes with significant changes in both the m5C modification and mRNA levels. Among these, GPRC5B emerged as a key prognostic gene, with its high expression and m5C hypermethylation significantly associated with poor survival in osteosarcoma patients. Functional experiments demonstrated that GPRC5B suppresses apoptosis and promotes osteosarcoma cell proliferation and migration. Mechanistically, NSUN2-mediated m5C modification upregulates GPRC5B expression, and the anti-apoptotic effects of NSUN2 are primarily dependent on its ability to modulate GPRC5B m5C modification and expression. Knockdown of GPRC5B partially rescues the anti-apoptotic effects of NSUN2, highlighting the critical role of GPRC5B in osteosarcoma survival. Our study identified an m5C-dependent NSUN2-GPRC5B regulatory axis, providing insights into osteosarcoma progression and revealing its therapeutic potential.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1322-1332"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475968","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":"Single-Cell Analysis Identified a Recurrent Malignant-Associated Transcriptional State in Colorectal Cancer.","authors":"Sadahiro Iwabuchi, Kentaro Sawada, Motohiro Kojima, Miho Ozawa, Hiroya Taniguchi, Hideaki Bando, Kazumi Abe, Yuta Kuze, Kiyomi Imamura, Yukie Kashima, Yoshihiko Hirohashi, Atsushi Tajima, Toshihiko Torigoe, Yutaka Suzuki, Takayuki Yoshino, Shinichi Hashimoto","doi":"10.1111/cas.70335","DOIUrl":"10.1111/cas.70335","url":null,"abstract":"<p><p>Colorectal cancer (CRC) exhibits substantial molecular heterogeneity, yet detailed single-cell transcriptomic data from Japanese patients remain limited. Here, we performed single-cell RNA sequencing (scRNA-seq) on tumor tissues and adjacent normal tissues from four Japanese CRC patients to characterize malignant cell populations. We identified a common cancer-associated cell cluster observed across all four cases, characterized by high expression of the long noncoding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1). Further analysis revealed a marked decrease in Ras Association Domain Family Member 6 (RASSF6) expression within this cluster, despite clinical datasets reporting that elevated RASSF6 expression correlates with poor overall survival in Western cohorts. Reanalysis of publicly available bulk RNA-seq data from independent East Asian cohorts confirmed that RASSF6 expression was consistently reduced in tumor tissues compared with adjacent normal colon tissues, while KCNQ1OT1 expression showed no apparent differences across cohorts. Collectively, our single-cell analysis delineates a recurrent cancer-associated transcriptional state observed within this cohort and highlights distinct gene expression features that may be underappreciated by bulk or population-averaged analyses, underscoring the value of single-cell profiling for refining molecular interpretations of CRC.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1397-1411"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345530","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":"TGF-β Inhibitor Potentiates Osimertinib-Induced Anti-Tumor Immunity in Egfr-Mutant Lung Cancer.","authors":"Tadahiro Kuribayashi, Jun Nishimura, Sachi Okawa, Masataka Taoka, Shunta Mori, Takaaki Tanaka, Tomoka Nishimura, Ayako Morita, Naofumi Hara, Kiichiro Ninomiya, Go Makimoto, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Yosuke Togashi, Yoshinobu Maeda, Katsuyuki Kiura, Kadoaki Ohashi","doi":"10.1111/cas.70352","DOIUrl":"10.1111/cas.70352","url":null,"abstract":"<p><p>Immunotherapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) remains challenging. We previously found that EGFR-tyrosine kinase inhibitors induced antitumor immunity but also triggered immunosuppressive cytokines, including transforming growth factor-β (TGF-β), in Egfr-mutant lung cancer. Here, we investigate whether TGF-β inhibition potentiates osimertinib-induced antitumor immunity using a syngeneic mouse model of Egfr-mutated lung cancer, with cancer cells subcutaneously transplanted into wild-type C57BL/6J mice. We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). Changes in the tumor microenvironment during treatment were assessed using immunohistochemical staining, western blot analysis, and flow cytometry. We found that TGF-β expression was upregulated in the tumor treated with osimertinib. Nintedanib monotherapy showed no significant antitumor effect, whereas osimertinib combined with nintedanib significantly potentiates the antitumor effect compared with osimertinib monotherapy in vivo. Crucially, no additive effect of nintedanib on osimertinib monotherapy was observed in vitro. Combination therapy with osimertinib and nintedanib significantly increased effector T cells (CD8⁺CD44⁺CD62L^-) and Granzyme B⁺ areas and decreased CD206⁺ cells, while significantly decreasing TGF-β and SMAD2/3 expression. Similar effects were observed with vactosertib but not with a vascular endothelial growth factor receptor 2 inhibitor. In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1260-1272"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311515","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":"Associations Between Obesity, Diabetes Mellitus, and Pancreatic Cancer in the Japanese Population: A Mendelian Randomization Study.","authors":"Yingsong Lin, Haruki Sasado, Naoki Sasahira, Makoto Ueno, Hiroshi Ishii, Naoto Egawa, Yasushi Adachi, Masato Ozaka, Satoshi Kobayashi, Yuriko N Koyanagi, Sayaka Yamamoto, Hidemi Ito, Akira Narita, Mika Sakurai-Yageta, Takuji Okusaka, Aya Kuchiba, Teruhiko Yoshida, Fumihiko Matsuda, Yoichiro Kamatani, Shiori Nakano, Taiki Yamaji, Norie Sawada, Aya Kadota, Kiyonori Kuriki, Takeshi Watanabe, Nobuo Fuse, Kengo Kinoshita, Naoki Nakaya, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Kozo Tanno, Ken Suzuki, Toshimasa Yamauchi, Takashi Kadowaki, Motoki Iwasaki, Sho Nakamura, Atsushi Hozawa, Atsushi Shimizu, Shogo Kikuchi, Masahiro Nakatochi, Keitaro Matsuo","doi":"10.1111/cas.70344","DOIUrl":"10.1111/cas.70344","url":null,"abstract":"<p><p>The association between body mass index (BMI) and pancreatic cancer remains elusive in Asian populations. Clarifying the causal relationship between type 2 diabetes (T2D) and pancreatic cancer warrants triangulation of evidence, with Mendelian Randomization (MR) providing a robust approach. A two-sample, multivariable MR analysis was performed to investigate the associations between BMI, T2D, and pancreatic cancer risk in the Japanese population. Single nucleotide polymorphisms (SNPs) associated with BMI and T2D were selected from the Genome-Wide Association Study (GWAS) Catalog, and summary statistics for pancreatic cancer were derived from our previous GWAS in the Japanese population. MR analyses were performed using a random-effects inverse variance-weighted (IVW) method as well as sensitivity analyses. Genetic predisposition to T2D, assessed using 891 SNPs, was associated with increased pancreatic cancer risk (IVW odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.08-1.25 per 1-unit increase in the ln odds of T2D). MR-Egger and weighted median MR analyses yielded similar results. By contrast, genetically indexed BMI showed no association with pancreatic cancer risk (IVW OR: 1.00; 95% CI: 0.95-1.04 per 1 kg/m² increase). The association between T2D and pancreatic cancer remained significant after adjusting for BMI (OR: 1.15; 95% CI: 1.07-1.24), while BMI was not significant in univariable or multivariable analyses. Our MR study supports a modest causal association of T2D, independent of BMI, with pancreatic cancer risk.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1446-1454"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221572","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":"SMURF1 Regulates CTCF-HOXA10 Axis and Promotes Tumor Progression in Nasopharyngeal Carcinoma.","authors":"Ying Jin, Tian Zhang, Zhimin Wu, Yuanshan Liang, Yiting Jiang, Guodong Yu","doi":"10.1111/cas.70353","DOIUrl":"10.1111/cas.70353","url":null,"abstract":"<p><p>The aberrant upregulation of Homeobox A10 (HOXA10) has been implicated in the progression of nasopharyngeal carcinoma (NPC), but the mechanisms driving its upregulation are not fully elucidated. This study demonstrated that the E3 ubiquitin ligase SMAD ubiquitination regulatory factor 1 (SMURF1) promoted the ubiquitin-mediated degradation of CCCTC-binding factor (CTCF), thereby alleviating CTCF-mediated transcriptional repression on HOXA10. Consequently, elevated HOXA10 expression contributed to tumor progression in NPC. We confirmed that HOXA10 was significantly upregulated in NPC and promoted malignant phenotypes of NPC cells. CTCF was identified as a direct transcriptional repressor of HOXA10 and was downregulated in NPC. Moreover, SMURF1 was found to be increased in NPC, where it directly bound to CTCF and regulated its protein stability. Specifically, SMURF1 promoted K48-linked ubiquitination degradation of CTCF. In vitro functional assays revealed that SMURF1 knockdown inhibited NPC cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In vivo experiments further confirmed that SMURF1 knockdown suppressed NPC tumor growth and lung metastasis, accompanied by increased CTCF expression and decreased HOXA10 level in both tumor and lung tissues. Collectively, these findings revealed the SMURF1/CTCF/HOXA10 axis as a crucial mechanism in NPC pathogenesis, positioning SMURF1 as a promising therapeutic target for intervention.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1346-1361"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147349189","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":"FOLFIRINOX vs. Gemcitabine/Nab-Paclitaxel for Pancreatic Cancer by BRCA2 and TMB Status: A Japanese C-CAT Database Study.","authors":"Kazuyuki Mizuno, Takuya Ishikawa, Takanori Ito, Yuko Takano, Osamu Maeda, Hiroki Kawashima, Yuichi Ando","doi":"10.1111/cas.70351","DOIUrl":"10.1111/cas.70351","url":null,"abstract":"<p><p>The clinical impact of BRCA2 variants and tumor mutational burden (TMB) on first-line regimen selection-FOLFIRINOX (FFX) versus gemcitabine plus nab-paclitaxel (GnP)-for pancreatic ductal adenocarcinoma (PDAC) remains unclear. Using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, we analyzed patients with unresectable or recurrent PDAC treated with first-line FFX or GnP. Overall survival (OS) and time to treatment failure (TTF) were compared, stratified by BRCA2 pathogenic variants (PVs) and TMB status. A total of 4356 patients were included. In the overall population, GnP was associated with superior adjusted OS compared with FFX (adjusted hazard ratio [HR] 0.90, p = 0.015), while TTF was comparable. In patients with BRCA2 PVs (3.3%), FFX demonstrated a significantly higher objective response rate (66.7% vs. 33.3%) and longer TTF compared with GnP. However, OS in patients with BRCA2 PVs was comparable between the two regimens (HR 1.11, p = 0.665). Among patients with BRCA2 PVs treated with GnP, OS was numerically longer with second-line FFX than with nal-IRI/5-FU/leucovorin (HR 0.51; p = 0.119). In patients without BRCA2 PVs, OS was longer with GnP. TMB-high status (2.9%) predicted significantly longer OS regardless of the first-line regimen (HR 0.64, p < 0.001). In conclusion, GnP was associated with superior adjusted OS in the overall population. In BRCA2 PV tumors, greater tumor shrinkage with first-line FFX did not translate into longer OS, underscoring the importance of sequencing strategies that ensure timely exposure to platinum-based therapy. TMB-high tumors may benefit from timely access to immunotherapy.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1422-1433"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379320","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":"Expression of Glycoprotein B (gB) Correlates With Poor Prognosis in Nasopharyngeal Carcinoma.","authors":"Shigetaka Komura, Satoru Kondo, Hideya Kawasaki, Shinji Watanabe, Satoshi Yamada, Hirotomo Dochi, Han Gia Nguyen, Isao Ohta, Makiko Moriyama-Kita, Masaki Fukuyo, Kousho Wakae, Yuki Kitagawa, Harue Mizokami, Luyao Liu, Nobuyuki Hirai, Eiji Kobayashi, Takayoshi Ueno, Yosuke Nakanishi, Kazuhira Endo, Hisashi Sugimoto, Naohiro Wakisaka, Rikinari Hanayama, Kiyoshi Misawa, Atsushi Kaneda, Tomokazu Yoshizaki","doi":"10.1111/cas.70341","DOIUrl":"10.1111/cas.70341","url":null,"abstract":"<p><p>The Epstein-Barr virus (EBV) has two life cycles: latent and lytic. Previously, the latent cycle had been considered more relevant to EBV-associated epithelial malignancies, including nasopharyngeal carcinoma (NPC), whereas the lytic cycle, which ultimately leads to the death of host cells, had not been considered. However, recent studies have revealed that abortive lytic infections, in which the lytic cycle halts midway, avoids host cell death and contributes to tumorigenesis and tumor growth. However, the progression of the lytic cycle in NPC and its association with viral replication remain unclear. This study aimed to perform morphological analyses of EBV-positive NPC cell lines and clinical NPC biopsy samples using transmission electron microscopy, NanoSuit-correlative light and electron microscopy, and scanning ion conductance microscopy. Virion-like particles were observed in lytically induced EBV-positive NPC cell lines using time-lapse imaging to capture their release. These particles were also detected in clinical NPC samples using electron microscopy. Immunohistochemical analysis with the glycoprotein B (gB) antibody revealed a strong association between gB expression and poor prognosis. In conclusion, lytic infections with EBV replication occur in NPC, and the frequency of EBV replication is significantly associated with poor prognosis.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1481-1496"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491914","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":"Transcriptional Reinforcement of the HER2-RAS Network in HER2-Positive Gastric Cancer: The RUNX-SOS1 Axis in Context.","authors":"Tatsuya Masuda, Takayoshi Watanabe, Toshinori Ozaki, Yasuhiko Kamikubo","doi":"10.1111/cas.70364","DOIUrl":"10.1111/cas.70364","url":null,"abstract":"<p><p>HER2-positive gastric cancer represents a distinct molecular subtype characterized by chromosomal instability, variable HER2 amplification, and substantial intratumoral heterogeneity. Although HER2-targeted therapies have improved clinical outcomes, therapeutic resistance commonly develops and limits long-term benefit. Established resistance mechanisms include bypass signaling through alternative receptor tyrosine kinases, reactivation of downstream pathways such as PI3K-AKT and MAPK, and dynamic changes in HER2 expression during treatment. These findings underscore the complexity of signaling regulation in HER2-driven tumors and indicate that mechanisms beyond receptor-level inhibition contribute to persistent oncogenic signaling. In this review, we examine the concept of transcriptional reinforcement within the HER2-RAS signaling network and discuss RUNX-dependent regulation of SOS1 as a downstream mechanism that may sustain signaling activity. We position this regulatory axis within the broader landscape of established resistance mechanisms and emerging therapeutic strategies, including antibody-drug conjugates, kinase inhibitors, and rational combination approaches. By integrating canonical resistance pathways with transcriptional regulation, this review provides a balanced perspective on how downstream regulatory processes may influence therapeutic response in HER2-positive gastric cancer.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1235-1243"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475971","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}