International Journal of Cancer最新文献

{"title":"Cohesin mutations and chromatin changes in cancer.","authors":"Ariel D Swett, Zuzana Tothova","doi":"10.1002/ijc.35378","DOIUrl":"https://doi.org/10.1002/ijc.35378","url":null,"abstract":"<p><p>The identification of recurrent mutations in genes encoding the cohesin complex in cancer was among the most unexpected findings from cancer exome sequencing studies. Cohesin is a multi-subunit protein complex that is essential for sister chromatid cohesion, three-dimensional chromosome organization, DNA damage repair, and gene regulation. It forms a ring around DNA, with four structural subunits, SMC1A, SMC3, RAD21, and either STAG1 or STAG2. In particular, the cohesin subunit STAG2 is one of only 12 human genes to be significantly mutated in four or more distinct types of cancer. Cohesin mutations are typically heterozygous and result in haploinsufficiency and/or loss-of-function, and although they might be expected to cause defects in chromosome segregation, the sister chromatid cohesion function of the complex is unlikely the driving mechanism of tumorigenesis, given the lack of aneuploidy in cohesin-mutant cancers. In this review, we will focus on the prevalence of somatic mutations in cohesin subunits across different cancer types, the influence of these mutations on chromatin organization and gene regulation, the resulting cellular and disease phenotypes, and the therapeutic potential of targeting the mutant cohesin complex.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583894","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}

{"title":"DCLK1 in gastrointestinal cancer: A driver of tumor progression and a promising therapeutic target","authors":"Ahmad Ghorbani Vanan,&nbsp;Soheil Vesal,&nbsp;Parmida Seraj,&nbsp;Mohammad Amin Ghezel,&nbsp;Pooya Eini,&nbsp;Maryam talebileili,&nbsp;Zeynab Asgari,&nbsp;Safa Tahmasebi,&nbsp;Mehrdad Hashemi,&nbsp;Afshin Taheriazam","doi":"10.1002/ijc.35365","DOIUrl":"10.1002/ijc.35365","url":null,"abstract":"<p>Cancers of the gastrointestinal (GI) tract, including colorectal, pancreatic, and hepatocellular carcinomas, represent a significant global health burden due to their high incidence and mortality rates. Doublecortin-like kinase 1 (DCLK1), initially identified for its role in neurogenesis, has emerged as a crucial player in GI cancer progression. This review comprehensively examines the multifaceted roles of DCLK1 in GI cancers, focusing on its structural isoforms, functions in normal and inflammatory states, and contributions to cancer progression and metastasis. DCLK1 is overexpressed in various GI cancers and is associated with poor prognosis, enhanced tumorigenic potential, and increased metastatic capacity. The review discusses the molecular mechanisms through which DCLK1 influences cancer stem cell maintenance, epithelial-mesenchymal transition (EMT), and cell survival pathways, as well as its interactions with key signaling pathways such as Notch, WNT/β-catenin, and NF-κB. The potential of DCLK1 as a therapeutic target is also explored, highlighting preclinical and early clinical efforts to inhibit its function using small molecule inhibitors or monoclonal antibodies. Despite significant advancements, further research is needed to fully elucidate DCLK1's role in GI cancers and to develop effective therapeutic strategies targeting this protein.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"156 11","pages":"2068-2086"},"PeriodicalIF":5.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583895","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}

{"title":"Delineation of monocytic and early-stage myeloid-derived suppressor cells in the peripheral blood of patients with hepatocarcinoma.","authors":"Marta Chivite-Lacaba, Iago Justo, Alberto Utrero-Rico, Oscar Caso, Cecilia González-Cuadrado, Manuel J Del Rey, Rocio Laguna-Goya, Javier Arroyo-Ródenas, Ángel Alfocea-Molina, Carlota C Ruigómez-Martín, Manuel Serrano, Lorena Pascual-Palacios, María Esther Mancebo, Estela Paz-Artal","doi":"10.1002/ijc.35390","DOIUrl":"https://doi.org/10.1002/ijc.35390","url":null,"abstract":"<p><p>In patients with hepatocellular carcinoma (HCC), increased myeloid-derived suppressor cells (MDSC) relate to aggressiveness and poor prognosis. Favorable responses with immune checkpoint inhibitors demonstrate that HCC is susceptible to immune activation, suggesting that the elimination of MDSC would provide therapeutic benefits. However, a global analysis of the different MDSC subsets in HCC is still missing. Here we phenotyped circulating myeloid cell subsets (monocytes, M-MDSC, PMN-MDSC and eMDSC) by flow cytometry in HCC and hepatocholangiocarcinoma patients and in healthy donors (HD). Isolated myeloid CD33⁺ cells were analyzed in immunosuppression assays, and cytokines were quantified in the supernatants. Arginase-1 activity (Arg-1) was analyzed in serum samples. All three proportions of MDSC, together with the immunosuppressive Arg-1, were significantly increased in HCC compared with HD. An important proportion of eMDSC expressed CD25, the IL-2 receptor α chain, and CD25⁺ eMDSC were also significantly expanded in HCC patients. HCC-CD33⁺ cells, enriched in M-MDSC and eMDSC, in vitro inhibited both CD4⁺ and CD8⁺ T cell proliferation and IL-2 production, and augmented IL-10, IL-6, and TNF-α. The correlation between the inhibition of T lymphocyte proliferation and M-MDSC was the strongest, while eMDSC or CD25⁺ eMDSC did not show antiproliferative capacity. Despite this functional difference, M-MDSC, CD25⁺ eMDSC, and CD25 expression in eMDSC were more prominent in advanced HCC as defined by a higher number of nodules, TNM stage, and alpha-fetoprotein level. This better delineation of M-MDSC and eMDSC phenotype and function in HCC could help to design therapies more likely to succeed in clinical trials.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571742","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}

{"title":"Correction to “Chronotherapy in head and neck cancer: A systematic review and meta-analysis”","authors":"","doi":"10.1002/ijc.35396","DOIUrl":"10.1002/ijc.35396","url":null,"abstract":"<p>Abusamak M, Abu-Samak A-A, Cai W, et al. Chronotherapy in head and neck cancer: a systematic review and meta-analysis. <i>Int J Cancer</i>. 2025;156(5):1015–1032. doi:10.1002/ijc.35234</p><p>In the article, there is an error in the acknowledgements.</p><p>The sentence reads:</p><p>The publication of this article was funded by the Qatar National Library.</p><p>This sentence should read:</p><p>Open Access funding provided by the Qatar National Library.</p><p>The online version of the article has been updated.</p><p>We apologize for this error.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"156 11","pages":"E15"},"PeriodicalIF":5.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.35396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571739","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":"Incorporation of Epstein–Barr viral variation implicates significance of Latent Membrane Protein 1 in survival prediction and prognostic subgrouping in Burkitt lymphoma","authors":"Isaac E. Kim Jr.,&nbsp;Cliff Oduor,&nbsp;Julian Stamp,&nbsp;Micah A. Luftig,&nbsp;Ann M. Moormann,&nbsp;Lorin Crawford,&nbsp;Jeffrey A. Bailey","doi":"10.1002/ijc.35384","DOIUrl":"10.1002/ijc.35384","url":null,"abstract":"<p>Although Epstein–Barr virus (EBV) plays a role in Burkitt lymphoma (BL) tumorigenesis, it is unclear if EBV genetic variation impacts clinical outcomes. From 130 publicly available whole-genome tumor sequences of EBV-positive BL patients, we used least absolute shrinkage and selection operator (LASSO) regression and Bayesian variable selection models within a Cox proportional hazards framework to select the top EBV variants, putative driver genes, and clinical features associated with patient survival time. These features were incorporated into survival prediction and prognostic subgrouping models. Our model yielded 22 EBV variants, including seven in latent membrane protein 1 (LMP1), as most associated with patient survival time. Using the top EBV variants, driver genes, and clinical features, we defined three prognostic subgroups that demonstrated differential survival rates, laying the foundation for incorporating EBV variants such as those in LMP1 as predictive biomarker candidates in future studies.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"156 11","pages":"2188-2199"},"PeriodicalIF":5.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565708","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}

{"title":"Targeting fatty acid oxidation: A potential strategy for treating gastrointestinal tumors.","authors":"Yingsong Zheng, Zhengchen Jiang, Li Yuan, Xiangdong Cheng, Weiyang He, Xiaodong Chen","doi":"10.1002/ijc.35380","DOIUrl":"https://doi.org/10.1002/ijc.35380","url":null,"abstract":"<p><p>Gastrointestinal cancers including esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), and colorectal cancer (CRC) are common and highly lethal types of cancer worldwide. Metabolic reprogramming plays a critical role in cancer progression and involves metabolic processes such as glucose and lipid metabolism. Fatty acid oxidation (FAO) has a profound impact on cancer, with many genes and cytokines influencing cancer cell initiation, development, metastasis, and resistance by regulating FAO. Additionally, FAO further promotes cancer progression by affecting the tumor microenvironment (TME). The role of FAO in gastrointestinal cancers has garnered increasing attention, and related anticancer drugs are currently being developed.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565709","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}

{"title":"Hypoxia-mediated high expression of TRIM15 promotes malignant progression of high-grade serous ovarian cancer through activation of AKT signaling pathway by K63 ubiquitination.","authors":"Wei Wei, Yang Zhang, Yibing Li, Jiazhen Huang, Fuli Kang, Shuang Tan, Lin Lin, Xiaohang Lu, Heng Wei, Ning Wang","doi":"10.1002/ijc.35387","DOIUrl":"https://doi.org/10.1002/ijc.35387","url":null,"abstract":"<p><p>The tripartite motif (TRIM) family member TRIM15 is an E3 ubiquitin ligase that is abnormally expressed in a variety of tumors, but its role and mechanism in high-grade serous ovarian cancer (HGSOC) are unclear. Here, we found for the first time that TRIM15 was upregulated in HGSOC and was associated with poor overall survival. Functional experiments showed that TRIM15 drove the proliferation of HGSOC cells and inhibited the apoptosis of tumor cells in vivo and in vitro. In terms of mechanism, we found that TRIM15 contributed to the malignant proliferation of HGSOC cells by promoting the activation of AKT and that there was a direct binding between them. TRIM15 induced lysine-63 (K63) ubiquitination of AKT through its Ring domain, which in turn activated the AKT signaling pathway. In addition, TRIM15-mediated K63 ubiquitination occurs mainly in the pleckstrin homology (PH) domain of AKT. We further identified other proteins and their functions regulated by TRIM15 in HGSOC cells by ubiquitin proteomic analysis. Furthermore, hypoxia-inducible factor-1α promoted TRIM15 transcriptional activation by binding to the hypoxia response elements of the TRIM15 promoter. Our study suggests that TRIM15 induces K63 ubiquitination of the AKT PH domain through its Ring domain and activates the AKT signaling pathway, thereby promoting HGSOC progression. In addition, the abnormally high expression of TRIM15 was associated with the hypoxic microenvironment of HGSOC tissues.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536288","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}

{"title":"Global landscape of cervical cancer incidence and mortality in 2022 and predictions to 2030: The urgent need to address inequalities in cervical cancer.","authors":"Zhuang Li, Penglin Liu, Aijun Yin, Bingxin Zhang, Jiaqi Xu, Zhongshao Chen, Zhaoyang Zhang, Yawen Zhang, Shuaixin Wang, Lingliya Tang, Beihua Kong, Kun Song","doi":"10.1002/ijc.35369","DOIUrl":"https://doi.org/10.1002/ijc.35369","url":null,"abstract":"<p><p>Cervical cancer remains a major public health challenge worldwide, despite being largely preventable through effective interventions. Timely evidence regarding the global landscape of cervical cancer is crucial for measuring the magnitude of inequalities and monitoring progress towards cervical cancer elimination. We aimed to provide an updated overview of the global burden of cervical cancer using the GLOBOCAN 2022 database. Age-standardized rates of incidence and mortality were presented according to countries, 20 United Nations-defined world regions, and four-tier Human Development Index (HDI) levels. The predicted burden of cervical cancer for 2030 was calculated based on global demographic projections. Globally, an estimated 662,301 new cervical cancer cases and 348,874 deaths occurred in 2022. Substantial geographic disparities in cervical cancer burden existed across countries and world regions. Low HDI countries exhibited two times higher incidence rates and five times higher mortality rates, compared to very high HDI countries. For women aged 15-44 years, cervical cancer ranked among the top three most frequent cancers in 149 countries, and among the top three causes of cancer deaths in 154 countries. If 2022 rates remain unchanged, the global burden of cervical cancer was predicted to increase to 760,082 new cases (a 14.8% increase) and 411,035 deaths (a 17.8% increase) by 2030. Our findings highlight the persistent and widening geographic and socioeconomic inequalities in the burden of cervical cancer. There is an urgent need for tailored national strategies to address these inequalities and accelerate progress towards the goal of cervical cancer elimination.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536287","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}

{"title":"Induction of SOX17 with stimulation of WNT, TGF-beta, and FGF signaling drives embryonal carcinomas into the yolk-sac tumor lineage resulting in increased cisplatin resistance","authors":"Mara Kotthoff,&nbsp;Margaretha A. Skowron,&nbsp;Felix Bremmer,&nbsp;Fatma Parmaksiz,&nbsp;Pia Kretschmer,&nbsp;Alexa Stephan,&nbsp;Alexander Fichtner,&nbsp;Tobias Lautwein,&nbsp;Katharina Raba,&nbsp;Janina Fuß,&nbsp;Karl Köhrer,&nbsp;Daniel Nettersheim","doi":"10.1002/ijc.35385","DOIUrl":"10.1002/ijc.35385","url":null,"abstract":"<p>Relapsing germ cell tumor (GCT) patients often harbor components of the aggressive subtype yolk-sac tumor (YST), suggesting that YST formation is an escape mechanism under therapy. Nevertheless, the molecular mechanisms inducing YST development from its stem cell-like precursor embryonal carcinoma (EC) are largely unexplored. We demonstrated that the induction of the transcription factor SOX17 together with the stimulation of WNT, TGF-beta / Activin, and FGF signaling drives EC cells into the YST lineage. Single cell RNA sequencing revealed that this cell fate switch was accompanied by the upregulation of the typical YST factors <i>AFP</i>, <i>ANKRD1</i>, <i>APOA1</i>, <i>CST1</i>, <i>FOXA2</i>, <i>GATA6</i>, and <i>GPC3</i> and microRNAs, while pluripotency-related genes <i>NANOG</i>, <i>POU5F1</i>, and <i>SOX2</i> were downregulated. Chromatin immunoprecipitation followed by sequencing analysis revealed that SOX17 may act in concert with FOXA2 and GATA factors to initiate YST formation. Xenografting of the YST-like cells into nude mice led to the growth of mixed GCT with YST components, confirming that these cells are able to form a YST in vivo. Moreover, the expression of cisplatin resistance factors was induced in a subpopulation of YST-like cells, suggesting that the formation of a YST is accompanied by the acquisition of cisplatin resistance. Indeed, the YST-like cells presented as less sensitive to cisplatin than their parental cells. Our study deciphered the molecular mechanisms forcing EC to differentiate into the YST lineage, which is accompanied by the acquisition of cisplatin resistance, confirming that YST formation is an escape mechanism for GCT under therapy. Thus, GCT patients should be screened for YST elements under therapy to identify patients at risk of developing therapy resistance.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"156 11","pages":"2210-2224"},"PeriodicalIF":5.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.35385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536144","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":"RETRACTION: Circular RNA CEP128 Promotes Bladder Cancer Progression by Regulating Mir-145-5p/Myd88 via MAPK Signaling Pathway","authors":"","doi":"10.1002/ijc.35391","DOIUrl":"10.1002/ijc.35391","url":null,"abstract":"<p><b>RETRACTION:</b> <span>M. Sun</span>, <span>W. Zhao</span>, <span>Z. Chen</span>, <span>M. Li</span>, <span>S. Li</span>, <span>B. Wu</span> and <span>R. Bu</span>, “ <span>Circular RNA CEP128 Promotes Bladder Cancer Progression by Regulating Mir-145-5p/Myd88 via MAPK Signaling Pathway</span>,” <i>International Journal of Cancer</i> <span>145</span>, no. <span>8</span> (<span>2019</span>): <span>2170</span>–<span>2181</span>, https://doi.org/10.1002/ijc.32311.</p><p>The above article, published online on 02 April 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christoph Plass; the Union for International Cancer Control; and John Wiley &amp; Sons, Ltd. The retraction has been agreed following an investigation into concerns raised by a third party. The investigation identified flaws and inconsistencies between the methodology described and the results presented. The authors were contacted and invited to comment on these concerns and to provide relevant supporting documentation, but they did not respond. The editors consider the results unreproducible and have therefore decided to retract this article. The authors were informed of the retraction.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"156 11","pages":"E16"},"PeriodicalIF":5.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.35391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527801","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}