Cancer Science最新文献

Losartan Enhances Radiosensitivity by Reversing Immunosuppressive Tumor Microenvironment Induced by Radiotherapy in TNBC. 氯沙坦通过逆转三阴癌放疗诱导的免疫抑制肿瘤微环境增强放射敏感性。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-07 DOI: 10.1111/cas.70407

Xu Wang, Cuiwei Liu, Zihan Xia, Ting Hu, Yuting Li, Dan Han, Yunjie Song, Yuxi Ma, Yanxia Zhao

{"title":"Losartan Enhances Radiosensitivity by Reversing Immunosuppressive Tumor Microenvironment Induced by Radiotherapy in TNBC.","authors":"Xu Wang, Cuiwei Liu, Zihan Xia, Ting Hu, Yuting Li, Dan Han, Yunjie Song, Yuxi Ma, Yanxia Zhao","doi":"10.1111/cas.70407","DOIUrl":"https://doi.org/10.1111/cas.70407","url":null,"abstract":"Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with limited therapeutic options. Radiotherapy (RT) is a cornerstone of TNBC treatment; however, preclinical studies suggest that RT may both stimulate and suppress immune responses within the tumor microenvironment (TME). While RT can enhance immune responses, it may also induce an immunosuppressive TME, contributing to radioresistance. The renin-angiotensin system (RAS) is also involved in the immunosuppressive TME and tumor radioresistance. Previous research showed blocker of angiotensin II receptor (AGTR1), losartan, as a RAS inhibitor, could alleviate hypoxia, thereby enhancing RT efficacy. Our study shows that high levels of AGTR1 may confer a poor prognosis and radioresistance in TNBC, and innovatively demonstrates losartan could enhance the radiosensitivity of TNBC in an immune dependent way. Furthermore, we found losartan could inhibit tumor-associated macrophages (TAMs) polarizing towards M2 phenotype, impedes the immunosuppressive function of myeloid-derived suppressive cells (MDSCs) induced by RT, and ultimately up-regulates the number and function of tumor-infiltrating CD8+ T lymphocytes. Besides, RNA-seq data reveals losartan impedes JAK2/STAT1 signaling activation upon irradiation, suppresses the interferon-related DNA damage resistant signature (IRDS) expression and diminishes the immune suppressive factors PD-L1 and IDO induced by irradiation in TNBC cells. Collectively, in our study, we investigate the role of losartan in radiosensitization and demonstrate losartan could reverse the immunosuppressive TME induced by RT in TNBC, which suggests that losartan combined with RT may represent a promising strategy for the treatment of TNBC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Triple-Mutated HSV-1 Expressing Soluble B7-1 Plus CTLA-4 Blockade Suppresses Lymph Node Metastasis in Tongue Cancer. 表达可溶性B7-1 + CTLA-4阻断物的三突变HSV-1抑制舌癌淋巴结转移

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-05 DOI: 10.1111/cas.70410

Akinari Sugauchi, Toshihiro Uchihashi, Hirotaka Ito, Miwako Iwai, Yuzuri Tsurumaki Sato, Kyoko Kurioka, Sena Zeynep Usta, Minoru Tanaka, Mikihiko Kogo, Susumu Tanaka, Hiroshi Fukuhara, Tomoki Todo

{"title":"Triple-Mutated HSV-1 Expressing Soluble B7-1 Plus CTLA-4 Blockade Suppresses Lymph Node Metastasis in Tongue Cancer.","authors":"Akinari Sugauchi, Toshihiro Uchihashi, Hirotaka Ito, Miwako Iwai, Yuzuri Tsurumaki Sato, Kyoko Kurioka, Sena Zeynep Usta, Minoru Tanaka, Mikihiko Kogo, Susumu Tanaka, Hiroshi Fukuhara, Tomoki Todo","doi":"10.1111/cas.70410","DOIUrl":"https://doi.org/10.1111/cas.70410","url":null,"abstract":"Cervical lymph node metastasis is a major predictor of poor prognosis in patients with oral squamous cell carcinoma (OSCC), underscoring the need for therapies that effectively target metastatic spread. We previously reported that G47Δ, a third-generation oncolytic herpes simplex virus type 1 (HSV-1), rapidly traffics from tongue tumors to cervical lymph nodes and suppresses metastasis in murine models. Based on this lymphotropic property and the immunological significance of CD28-B7-1 interactions for T-cell activation, we pursue the potential of T-mB7-1, a new G47Δ-derived oncolytic HSV-1 expressing soluble murine B7-1. T-mB7-1 secreted soluble B7-1 in vitro without compromising cytopathic activity. In vivo, intratumoral T-mB7-1 suppressed tumor growth in the resistant KLN205-MUC1 subcutaneous model and prolonged survival in SCCVII orthotopic tongue tumors. In the KLN205-MUC1 orthotopic tongue cancer that exhibits rapid lymphatic metastasis, a single dose of T-mB7-1, but not the control virus T-01, significantly reduced cervical lymph node metastasis and improved survival. Repeated low-dose T-mB7-1 further caused near-complete suppression of lymph node metastasis and markedly extended survival. Flow cytometry showed both T-01 and T-mB7-1 induced CD69+ T-cell activation in cervical lymph nodes at 18 h, which was reduced with T-mB7-1 at 24 h. Importantly, combining T-mB7-1 with systemic CTLA-4 blockade markedly prolonged survival of mice harboring orthotopic KLN205-MUC1 tumors, with all treated mice surviving beyond 80 days in the otherwise fatal model. These findings demonstrate that soluble B7-1-expressing oncolytic HSV-1 combined with CTLA-4 blockade durably suppresses lymph node metastasis, providing a promising and minimally invasive strategy for regionally metastatic OSCC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Super-Enhancer Formation in Scirrhous Gastric CAFs, and the Presence of a Stromal Field in Non-Cancerous Tissues. 结缔组织中超增强子的形成和非癌组织中基质场的存在。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-03 DOI: 10.1111/cas.70408

Yoshimi Yasukawa, Naoko Hattori, Yu-Yu Liu, Masayuki Tobo, Genki Yamagishi, Takahiro Irie, Shigeki Sekine, Tohru Kiyono, Satoshi Yamashita, Yukinori Yamagata, Takaki Yoshikawa, Yasuyuki Seto, Toshikazu Ushijima

{"title":"Super-Enhancer Formation in Scirrhous Gastric CAFs, and the Presence of a Stromal Field in Non-Cancerous Tissues.","authors":"Yoshimi Yasukawa, Naoko Hattori, Yu-Yu Liu, Masayuki Tobo, Genki Yamagishi, Takahiro Irie, Shigeki Sekine, Tohru Kiyono, Satoshi Yamashita, Yukinori Yamagata, Takaki Yoshikawa, Yasuyuki Seto, Toshikazu Ushijima","doi":"10.1111/cas.70408","DOIUrl":"https://doi.org/10.1111/cas.70408","url":null,"abstract":"Scirrhous gastric cancer has aggressive clinical courses and is characterized by dominating cancer-associated fibroblasts (CAFs). However, the origin of scirrhous CAFs remains unclear, and we here aimed to explore the epigenetic basis for scirrhous CAFs and their origin. Conditioned medium (CM) from scirrhous CAFs was shown to have a marked effect (2-4 folds) on the migration of gastric cancer cells compared to that from non-scirrhous CAFs. The aggressive phenotype of scirrhous CAFs was associated with activation of TGFβ1 and NF-κB, along with increased expression of their downstream genes. Scirrhous CAFs had heavily acetylated super-enhancers, and therapeutic targeting of super-enhancers by a BET bromodomain inhibitor, mivebresib and JQ-1, markedly decreased their migration-promoting activity. Notably, in scirrhous gastric cancer patients, normal fibroblasts in non-cancerous tissues also had a strong migration-promoting effect. It was suggested that fibroblasts in the non-cancerous tissue of scirrhous gastric patients have already acquired tumor-promoting capacity, forming a stromal field for scirrhous gastric cancer although its spatial extent remains to be solved.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AKR1C3 Binds β-Trcp to Promote the Degradation of TFRC to Protect Hepatocellular Carcinoma From Ferroptosis. AKR1C3结合β-Trcp促进TFRC降解保护肝癌铁凋亡

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-02 DOI: 10.1111/cas.70403

Lei Qi, Jingyi Hua, Di Pan, Wanwan Yang, Geng Tian, Fangyu Ye, Lingxiang Liu, Yuhan Mao, Qinglong Guo, Haopeng Sun, Li Zhao

{"title":"AKR1C3 Binds β-Trcp to Promote the Degradation of TFRC to Protect Hepatocellular Carcinoma From Ferroptosis.","authors":"Lei Qi, Jingyi Hua, Di Pan, Wanwan Yang, Geng Tian, Fangyu Ye, Lingxiang Liu, Yuhan Mao, Qinglong Guo, Haopeng Sun, Li Zhao","doi":"10.1111/cas.70403","DOIUrl":"https://doi.org/10.1111/cas.70403","url":null,"abstract":"Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, represents a new potential therapeutic target in cancer. However, emerging evidence indicates that hepatocellular carcinoma (HCC) frequently exhibits resistance to ferroptosis induction, while the underlying molecular mechanism is poorly understood. Here, we found that aldo-keto reductase family 1 member C3 (AKR1C3), a protein highly expressed in ferroptosis-resistant HCC cells, negatively regulates ferroptosis in an enzyme-independent manner. Mechanistically, AKR1C3 promotes ubiquitin-proteasomal degradation of the transferrin receptor (TFRC), which is indispensable for cellular iron uptake. AKR1C3 knockdown restores TFRC expression, increases the level of labile iron pool, and sensitizes HCC cells to ferroptosis. Furthermore, AKR1C3 acts as a scaffolding protein to promote the degradation of TFRC and reduce iron uptake by promoting nuclear export of Beta-transducin repeats-containing proteins (β-TrCP) and its binding to TFRC. Notably, AKR1C3 is upregulated in NRF2-driven sorafenib-resistant HCC, and its inhibition reversed ferroptosis and sorafenib resistance. Our work uncovers AKR1C3 suppresses ferroptosis in HCC by promoting β-TrCP-mediated TFRC degradation, positioning AKR1C3 as a promising therapeutic target to enhance ferroptosis-based anticancer strategies.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

L1CAM Promotes the Infiltrative Properties of Patient-Derived Glioblastoma Cells. L1CAM促进患者源性胶质母细胞瘤细胞的浸润特性。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-08 DOI: 10.1111/cas.70359

Asako Katsuma, Daisuke Kanematsu, Yukako Handa, Tomoko Shofuda, Atsuyo Yamamoto, Kayo Nishitani, Zhize Xiao, Daisuke Kawauchi, Kentarou Baba, Naoyuki Inagaki, Yonehiro Kanemura

{"title":"L1CAM Promotes the Infiltrative Properties of Patient-Derived Glioblastoma Cells.","authors":"Asako Katsuma, Daisuke Kanematsu, Yukako Handa, Tomoko Shofuda, Atsuyo Yamamoto, Kayo Nishitani, Zhize Xiao, Daisuke Kawauchi, Kentarou Baba, Naoyuki Inagaki, Yonehiro Kanemura","doi":"10.1111/cas.70359","DOIUrl":"10.1111/cas.70359","url":null,"abstract":"L1CAM is a member of the immunoglobulin superfamily involved in cell adhesion, migration, and neural development. While several studies have shown an association between L1CAM and glioblastoma (GBM) cell motility, its mechanobiological function in patient-derived primary cultured GBM cells remains insufficiently understood. This study focuses on L1CAM-dependent motility mechanisms in patient-derived GBM cells at the single-cell level. Patient-derived GBM cells were established from GBM tissues using the neurosphere method. L1CAM expression was evaluated by qPCR, western blotting, flow cytometry, and immunocytochemistry. Cell motility was assessed by single-cell tracking. Functional assays included forced expression and antibody-mediated inhibition of L1CAM. Adhesion-clutch behavior and retrograde F-actin flow were analyzed. For in vivo assessment, doxycycline-inducible L1CAM-overexpressing GBM cells were transplanted into mouse brains. L1CAM-high GBM cells showed increased motility on laminin compared to L1CAM-low cells. Anti-L1CAM antibody suppressed migration of L1CAM-high GBM cells, whereas ectopic expression enhanced migration in L1CAM-low GBM cells. L1CAM-positive GBM cells preferentially migrated on laminin rather than fibronectin, while L1CAM-low cells showed no such difference, indicating L1CAM-dependent haptotaxis. Forced L1CAM expression reduced retrograde actin flow velocity and promoted adhesion-clutch formation. In vivo, GBM cells with L1CAM overexpression displayed greater infiltrative capacity 12 weeks posttransplantation. L1CAM expression on GBM cells' surface regulates cell motility through adhesion-clutch mechanisms and substrate sensing. These mechanobiological features suggest that targeting L1CAM may serve as a promising strategy to suppress GBM cells infiltration and improve GBM treatment outcomes.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1380-1396"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379324","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}

引用次数: 0

RETRACTION: Frequent Alterations of the Candidate Genes hMLH1, ITGA9 and RBSP3 in Early Dysplastic Lesions of Head and Neck: Clinical and Prognostic Significance. 撤回：候选基因hMLH1、ITGA9和RBSP3在头颈部早期发育不良病变中的频繁改变：临床和预后意义。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-19 DOI: 10.1111/cas.70372

{"title":"RETRACTION: Frequent Alterations of the Candidate Genes hMLH1, ITGA9 and RBSP3 in Early Dysplastic Lesions of Head and Neck: Clinical and Prognostic Significance.","authors":"","doi":"10.1111/cas.70372","DOIUrl":"10.1111/cas.70372","url":null,"abstract":"Retraction: A. Ghosh, S. Ghosh, G.P. Maiti, M.G. Sabbir, E.R. Zabarovsky, A. Roy, S. Roychoudhury, and C.K. Panda, \"Frequent Alterations of the Candidate Genes hMLH1, ITGA9 and RBSP3 in Early Dysplastic Lesions of Head and Neck: Clinical and Prognostic Significance,\" Cancer Science 101, no. 6 (2010): 1511-1520, https://doi.org/10.1111/j.1349-7006.2010.01551.x. The above article, published online on 19 May 2010 in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley & Sons Australia, Ltd. A third party contacted the journal with concerns about duplicated images in the figures. Following an investigation, multiple duplications were found throughout Figures 2A, 3B, 4B, and supporting information Figure 2. Additionally, portions of some figures were duplicated in later articles by some of the same authors: Figure 2A in Dasgupta et al. 2016 (https://doi.org/10.2217/fon-2016-0289); Figures 2A and 3A in Ghosh et al. 2011 (https://doi.org/10.1245/s10434-011-1991-x); and Figure 3A in Bhattacharya et al. 2013 (https://doi.org/10.1245/s10434-012-2715-6). Due to the scope of the errors, the editor has lost confidence in the results reported, and therefore the article must be retracted. The authors have been informed of this decision.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1524"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488024","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}

引用次数: 0

Glucose Metabolism Regulating Colorectal Cancer Initiation and Progression. 糖代谢调节结直肠癌的发生和发展。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-06 DOI: 10.1111/cas.70357

Meiyi Lin, Junpeng Cui

引用次数: 0

HTLV-1 Tax Reshapes the DNA-Binding Pattern of Transcription Factor IRF4 and Disrupts Host Gene Regulation. HTLV-1 Tax重塑转录因子IRF4的dna结合模式并破坏宿主基因调控

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-02-25 DOI: 10.1111/cas.70349

Shu Tosaka, Jun Mizuike, Motomu Yano, Kaoru Uchimaru, Makoto Yamagishi

{"title":"HTLV-1 Tax Reshapes the DNA-Binding Pattern of Transcription Factor IRF4 and Disrupts Host Gene Regulation.","authors":"Shu Tosaka, Jun Mizuike, Motomu Yano, Kaoru Uchimaru, Makoto Yamagishi","doi":"10.1111/cas.70349","DOIUrl":"10.1111/cas.70349","url":null,"abstract":"Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy, and its viral transactivator Tax is central to disrupting host transcriptional control. Although individual interactions between Tax and host factors have been investigated, their global network and functional impact remain unclear. In this study, we performed proteomic analyses of Tax-associated complexes in HTLV-1-infected T-cells and mapped interactions between host factors and Tax. In addition to known nuclear factor kappa B (NF-κB) regulators, we identified the transcription factor interferon regulatory factor 4 (IRF4) as a novel interactor. Co-immunoprecipitation experiments confirmed Tax-IRF4 binding, and chromatin profiling revealed that Tax reprograms genome-wide IRF4 occupancy. In infected T-cells, IRF4 was enriched in super-enhancer (SE) regions, where Tax, IRF4, and NF-κB factors colocalized at ATL-related loci, and this was accompanied by histone acetylation changes and transcriptional activation. Functionally, Tax and IRF4 co-expression cooperatively restructured chromatin accessibility and induced aberrant gene expression programs. Moreover, ATL-associated IRF4 mutants (K59R, L70V, and S114N) partially reproduced Tax-driven chromatin remodeling and transcriptional reprogramming, suggesting that convergent mechanisms drive leukemogenesis. Collectively, these findings demonstrate that Tax exploits IRF4 to establish a novel regulatory mechanism. This interaction drives widespread epigenomic reprogramming in HTLV-1-infected T-cells. Overall, our study underscores the central role of Tax in IRF4 exploitation to induce infection-specific epigenomic changes, which offers novel insights into ATL pathogenesis and therapeutic strategies.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1497-1509"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285921","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}

引用次数: 0

Early-Onset Digestive System Cancers: Risk Factors and Clinicopathological and Molecular Features Across Organ Sites. 早发性消化系统癌症：跨器官部位的危险因素、临床病理和分子特征。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-18 DOI: 10.1111/cas.70363

Nobuhiro Nakazawa, Satoko Ugai, Atsushi Kondo, Kosuke Matsuda, Shu Kato, Genki Usui, Shiori Tanaka, Hwa-Young Lee, Xinyuan Zhang, Hideo Miyagawa, Mai Chan Lau, Hiroshi Saeki, Yukihide Kanemitsu, Andrew T Chan, Shuji Ogino, Minkyo Song, Juha P Väyrynen, Tomotaka Ugai

{"title":"Early-Onset Digestive System Cancers: Risk Factors and Clinicopathological and Molecular Features Across Organ Sites.","authors":"Nobuhiro Nakazawa, Satoko Ugai, Atsushi Kondo, Kosuke Matsuda, Shu Kato, Genki Usui, Shiori Tanaka, Hwa-Young Lee, Xinyuan Zhang, Hideo Miyagawa, Mai Chan Lau, Hiroshi Saeki, Yukihide Kanemitsu, Andrew T Chan, Shuji Ogino, Minkyo Song, Juha P Väyrynen, Tomotaka Ugai","doi":"10.1111/cas.70363","DOIUrl":"10.1111/cas.70363","url":null,"abstract":"The incidence of early-onset cancers, commonly defined as cancers diagnosed before age 50 years, has been increasing globally over recent decades. In particular, the incidence of several early-onset digestive system cancers, including cancers of the esophagus, stomach, colorectum, liver, extrahepatic bile duct, gallbladder, and pancreas, has been reported to be increasing in multiple regions. To elucidate carcinogenic mechanisms and develop effective prevention, earlier detection, and treatment strategies, further evidence is needed on risk factors and clinical, pathological, and molecular characteristics. In this review, we summarize the current evidence on these characteristics, highlight shared and distinct features across organ sites, and discuss research opportunities to address the rising burden of early-onset digestive system cancers.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1223-1234"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482126","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}

引用次数: 0

Cholangiolocellular Component Predicts a Biologically Distinct Subgroup of Mass-Forming Intrahepatic Cholangiocarcinoma. 胆管细胞成分预测形成团块的肝内胆管癌的生物学独特亚群。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-02 DOI: 10.1111/cas.70348

Naoto Kubota, Ken Yamazaki, Yasuhito Arai, Minoru Esaki, Nobuyoshi Hiraoka, Hirofumi Shirakawa, Moriaki Tomikawa, Tatsuhiro Shibata, Michiie Sakamoto, Hidenori Ojima

{"title":"Cholangiolocellular Component Predicts a Biologically Distinct Subgroup of Mass-Forming Intrahepatic Cholangiocarcinoma.","authors":"Naoto Kubota, Ken Yamazaki, Yasuhito Arai, Minoru Esaki, Nobuyoshi Hiraoka, Hirofumi Shirakawa, Moriaki Tomikawa, Tatsuhiro Shibata, Michiie Sakamoto, Hidenori Ojima","doi":"10.1111/cas.70348","DOIUrl":"10.1111/cas.70348","url":null,"abstract":"Cholangiolocellular carcinoma (CLC) is a histopathological variant of primary liver tumor with unique morphologies, and intrahepatic cholangiocarcinomas (iCCAs) frequently contain a CLC component; however, the biological characteristics of iCCA with CLC remain undescribed. In this study, 36 mass-forming iCCAs (MF-iCCAs), histologically small-duct type iCCA, were classified into CLC(+) iCCAs and CLC(-) iCCAs by the presence/absence of the CLC component. Two genetic subgroups were generated using highly expressed genes in CLC(+) iCCA and CLC(-) iCCA. As the results of clinicopathological and genetic analyses, CLC(+) iCCA had better overall survival and upregulation of stromal- and oxidation-related genes, whereas CLC(-) iCCA showed upregulation of proliferation- and hypoxia-related genes. Two genetic subgroups of iCCA were identified: iCCA-G1, which was related to CLC, and iCCA-G2, which was unrelated to CLC. iCCA-G1 comprised all 14 CLC(+) iCCAs [CLC(+)G1] and 7 of 19 CLC(-) iCCAs [CLC(-)G1], whereas iCCA-G2 was composed only of CLC(-) iCCAs [CLC(-)G2]. CLC(+)G1 and CLC(-)G1 exhibited similar patterns of somatic gene alterations compared with CLC(-)G2. Angiogenesis-related genes were upregulated in CLC(+)G1, and the number of tumor vessels was larger in CLC(+)G1, followed by CLC(-)G1, compared with CLC(-)G2. Further, SPP1 (encoding osteopontin) was identified as a highly expressed angiogenesis-related gene in CLC(+) iCCA. Immunohistochemical expression of osteopontin was high in CLC(+) iCCA, showing apical and/or cytoplasmic expression patterns, which should facilitate the histopathological classification of iCCA-G1 and iCCA-G2. CLC component is useful for predicting a distinct genetic subgroup of MF-iCCA with better prognosis, high angiogenesis, and different gene alteration patterns, indicating different carcinogenic pathways of MF-iCCA.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1510-1523"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345488","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}

引用次数: 0