Carcinogenesis最新文献

{"title":"Correction: Role of C9orf140 in the promotion of colorectal cancer progression and mechanisms of its upregulation via activation of STAT5, β-catenin and EZH2.","authors":"","doi":"10.1093/carcin/bgag036","DOIUrl":"https://doi.org/10.1093/carcin/bgag036","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: miR-720 inhibits tumor invasion and migration in breast cancer by targeting TWIST1.","authors":"","doi":"10.1093/carcin/bgag041","DOIUrl":"https://doi.org/10.1093/carcin/bgag041","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why a response from the tobacco industry is cause for satisfaction prior to being placed where it belongs.","authors":"Bernard W Stewart","doi":"10.1093/carcin/bgag060","DOIUrl":"10.1093/carcin/bgag060","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLN4924 enhances RSL3-induced ferroptosis sensitivity in glioblastoma via inhibiting the STAT3/GPX4 axis.","authors":"Zhou Jing, Fangyuan Wang, Hao Li, Bingqi Lu, Zian Li, Wulong Liang, Xudong Fu, Xinjun Wang","doi":"10.1093/carcin/bgag058","DOIUrl":"10.1093/carcin/bgag058","url":null,"abstract":"<p><p>Glioblastoma (GBM) is one of the most aggressive and treatment-resistant tumors of the central nervous system, demanding innovative therapeutic strategies. Ferroptosis, an iron-driven lipid peroxidation-dependent cell death, has emerged as a potential means to overcome resistance, with glutathione peroxidase 4 (GPX4) as its key suppressor. MLN4924 (pevonedistat), a first-in-class inhibitor of neddylation currently in clinical trials, has shown strong antitumor activity across multiple malignancies. However, its role in ferroptosis regulation and the underlying molecular mechanisms remain poorly defined. Here, we show that MLN4924 induces ferroptosis, with GPX4 emerging as a central regulatory node. GPX4 expression is elevated in gliomas compared to normal brains, and its higher levels correlate with increased grades and worse patient prognosis. MLN4924 downregulates GPX4 mRNA by suppressing STAT3 signaling, whereas RSL3 directly inhibits GPX4 enzymatic activity. The combination of MLN4924 and RSL3 synergistically potentiates ferroptosis and, in vivo, suppresses subcutaneous tumor growth with a considerable biosafety. Collectively, these findings identify GPX4 as the principal mediator of MLN4924-induced ferroptosis and establish that dual targeting of GPX4 transcription and activity represents a promising therapeutic strategy for GBM.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asbestos exposure induces malignant-like phenotypes via minority MOMP and displays characteristics of drug-tolerant persister cells.","authors":"Jaylon Aggison, Cristian Medina, Siqi Wu, Naren Li, Francisco Molina-Pelayo, Jessica Ji, Mickael Farouk Gergeis, Ritika Raj, Yuan Xu, R Taylor Ripley","doi":"10.1093/carcin/bgag030","DOIUrl":"10.1093/carcin/bgag030","url":null,"abstract":"<p><p>Pleural mesothelioma usually occurs many years after asbestos fiber exposure; yet the mechanisms that convert chronic damage into malignancy remain unclear. Asbestos fibers induce persistent oxidative and genomic stress that should activate apoptosis via mitochondrial outer membrane permeabilization (MOMP). MOMP normally triggers cytochrome c (cyt c) release as well as mitochondrially derived damage-associated molecular patterns, resulting in downstream caspase activation, which leads to DNA damage and cell death. With sublethal activation, a phenomenon known as an \"incomplete or minority MOMP (mMOMP)\" occurs in which the cell survives the damage, enabling retention and propagation of somatic mutations. We tested whether prolonged asbestos fiber exposure drives mMOMP in the mesothelial cells, MeT-5A. After culturing the cells for 6 months with chrysotile asbestos fibers or crocidolite asbestos fibers, we observed an increase in clonogenicity, migration, and invasion, suggesting that transformation to a malignant-like phenotype was occurring. Next, we found increases in reactive oxygen species (ROS) production, cyt c release, and γH2AX phosphorylation without activation of caspase-3 and apoptotic induction. These cellular features are consistent with mMOMP. Additionally, an anti-apoptotic, mitochondrial protein, myeloid cell leukemia-1 was upregulated by asbestos and enabled mMOMP by preventing MOMP. Furthermore, we observed that asbestos-induced mMOMP was associated with features of drug-tolerant persister cells. mMOMP facilitates avoidance of apoptosis by mesothelial cells while acquiring malignant traits. Our study indicates that mMOMP is a mechanism that promotes carcinogenesis, mitochondrial changes, and metabolic reprogramming. These findings offer a foundation for future therapeutic investigations.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Air pollution and early-onset lung cancer: from environmental carcinogenesis to early intervention strategies.","authors":"Yan-Yun Gao, Jiao-Jiao Xu, Yu-Xin Wu, Hong-Mei Xu, Gui-Zhen Wang, Guang-Biao Zhou","doi":"10.1093/carcin/bgag070","DOIUrl":"10.1093/carcin/bgag070","url":null,"abstract":"<p><p>Air pollution remains a global public health challenge, with nearly the entire global population (99%) breathing air that exceeds World Health Organization guideline limits-annual means of 5 μg/m3 for PM2.5 and 15 μg/m3 for PM10. Both household and ambient air pollution are classified as Group 1 carcinogens and contain hazardous components, including polycyclic aromatic hydrocarbons, heavy metals, and volatile organic compounds. Exposure contributes to a broad spectrum of systemic diseases and is responsible for more than 14% of global lung cancer deaths while also elevating risks for breast, gastrointestinal, and brain cancers. Mechanistically, air pollutants drive early lung carcinogenesis through intrinsic genomic instability, manifesting as DNA damage, telomere dysfunction, mitochondrial impairment, and specific mutational signatures, alongside epigenetic dysregulation. Concurrently, they foster a tumor-promoting niche via chronic inflammation mediated by CXCL13 and IL-1β and facilitate early immune evasion through activation of the PD-L1 and CD47-SIRPα axes. In addition, air pollution disrupts the respiratory-gut microbiome, reducing microbial diversity and promoting pathogenic enrichment. A range of early biomarkers-including genomic, epigenomic, inflammatory, and microbiome profiles-have been validated for preventive interventions, with multimarker combinations demonstrating improved efficacy. Multiple chemopreventive targets have also been identified to counteract oxidative stress, inflammation, and immune evasion. Looking ahead, research priorities should include exploring gene-environment interactions, clinically validating biomarkers and therapeutic targets, translating basic discoveries into clinical practice, and developing precision prevention strategies for high-risk populations. Ultimately, integrating biomarker-guided early detection with multi-target chemoprevention will be essential to reducing the global burden of air pollution-induced early-onset lung cancer.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclic adenosine monophosphate signaling pathway in tumor-associated macrophages: molecular mechanisms and tumor immunotherapy.","authors":"Yi Liu, Shuai Li, Wei Li, Mengting Zhou, Jie Liang, Xiaoli Liu, Xiao Wang, Yuanzhen Guo, Zhen Li, Bei Zhang, Luoyang Wang","doi":"10.1093/carcin/bgag026","DOIUrl":"10.1093/carcin/bgag026","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are the core innate immune cells in the tumor microenvironment (TME), and their phenotypic polarization and functional reprogramming determine the orientation of the tumor immune microenvironment and the efficacy of immunotherapy. As a key intracellular second messenger, cyclic adenosine monophosphate (cAMP) acts as a central hub regulating TAM function by activating two major downstream effector pathways: protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). This article systematically reviews the molecular mechanisms by which the cAMP-PKA/Epac signaling pathway regulates TAMs, the upstream regulatory factors in the TME, and targeted tumor immunotherapy strategies for this pathway. Studies have shown that cAMP mainly induces TAMs to polarize toward a protumor \"M2-like phenotype\" through two classical pathways: cAMP-PKA-cyclic AMP response element-binding protein (CREB) and cAMP-PKA-signal transducer and activator of transcription 3/6 (STAT3/6). Meanwhile, it enhances the immunosuppressive, proangiogenic, and profibrotic functions of TAMs via the cAMP-Epac pathway, inhibition of nuclear factor kappa-B (NF-κB) signaling, and attenuation of M1 polarization. Furthermore, lactate and hypoxia-inducible factor-1α (HIF-1α) in the TME can further activate the intracellular cAMP signaling pathway in TAMs by activating G protein-coupled receptors (GPCRs) and regulating the expression of adenylate cyclase, forming a cascade regulatory network with cAMP that exacerbates tumor immunosuppression. In addition, targeting the cAMP metabolic process, the downstream PKA pathway, and key molecules such as CREB/STAT/NF-κB can effectively reverse the \"M2-like phenotype\" of TAMs and restore their antitumor functions. Combination with immune checkpoint inhibitors can also significantly enhance the efficacy of tumor immunotherapy. By summarizing the core mechanisms of the cAMP-TAM regulatory axis and targeted intervention strategies, this article provides theoretical references and potential target directions for the development of novel tumor immunotherapy regimens based on TAM reprogramming.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Climate change, the exposome, and early-onset carcinogenesis.","authors":"Sherry Price, Erin J Plenzler, James R Hébert","doi":"10.1093/carcin/bgag054","DOIUrl":"https://doi.org/10.1093/carcin/bgag054","url":null,"abstract":"<p><p>The incidence of early-onset cancers (diagnosis before 50 years of age) has been steadily increasing globally, presenting a significant public health challenge. While genetic predispositions play a role, most cancers cannot be traced to heritable components. Furthermore, the rapid rise in the incidence rates of these cancers strongly suggests the influence of environmental factors that constitute the \"exposome.\" This perspective article integrates recent findings linking climate change and broader planetary health challenges to pervasive inflammation in the development of chronic diseases, especially cancer. We propose that the complex interplay of anthropogenic climate change, biodiversity loss, environmental degradation, disruption of ecological systems, exposure to environmental pathogens and toxins, industrialized food systems, and consumption of suboptimal, proinflammatory diets containing high concentrations of ultra-processed foods, creates a procarcinogenic exposome that may be particularly important during critical developmental windows, leading to increased susceptibility to carcinogenesis relatively early in life. Framed through a planetary health perspective, this article synthesizes evidence on how large-scale ecological disruption alters the human exposome and contributes to chronic inflammation, metabolic dysregulation, immune dysfunction, and cellular damage, all recognized drivers of cancer development. Although our primary focus is on early-onset cancers, many of these mechanisms are relevant across the cancer continuum and may influence carcinogenesis throughout the life course. We highlight the need for transdisciplinary research and integrated solutions that address both individual behaviors and systemic environmental and policy changes to mitigate the growing burden of early-onset cancers.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.","authors":"Changmo Park, Tin Lok Wong, Stephanie Ma","doi":"10.1093/carcin/bgag040","DOIUrl":"10.1093/carcin/bgag040","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), accounting for nearly 90% of primary liver cancers, remains a major global health challenge due to late diagnosis and therapy resistance. Up to 50% of cases exhibit aberrant activation of the canonical Wnt/β-catenin pathway, driven by CTNNB1 mutations or inactivating alterations in AXIN1, adenomatous polyposis coli, or ZNRF3, which are mutually exclusive. This hyperactivation has complex implications: it has been associated with drug resistance, larger tumors, epithelial-mesenchymal transition, vascular invasion, cancer stemness, and immune evasion, yet in some contexts, it correlates with a less aggressive, well-differentiated phenotype and improved survival. This heterogeneity highlights the need for further research to clarify its prognostic significance. This review explores recent mechanisms by which aberrant nuclear β-catenin accumulation fosters resistance to frontline tyrosine kinase inhibitors like sorafenib and lenvatinib through ferroptosis evasion, cancer stemness, and β-catenin stabilization. It also highlights how hyperactivated Wnt/β-catenin promotes an immunosuppressive \"cold\" tumor microenvironment, impairing immunotherapy efficacy. These include cytokine profile alterations, CD8+ T-cell exclusion, dendritic cell repression, and recruitment of immunosuppressive cells such as myeloid-derived suppressor cells, tumor-associated neutrophils, macrophages, and regulatory T cells. Recent preclinical studies show that combining Wnt inhibitors with immunotherapy or tyrosine kinase inhibitors can reprogram the tumor microenvironment, restore ferroptosis sensitivity, eradicate cancer stem cells, enhance CD8+ T-cell infiltration, boost antitumor immunity, and overcome resistance with minimal side effects. Targeting the Wnt/β-catenin pathway offers a promising strategy to transform HCC treatment and improve outcomes by exploiting this pathway as a key therapeutic vulnerability.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring potential associations between low-dose cardiac catheterization radiation and blood microRNA changes in children with congenital heart disease.","authors":"Jonica Campolo, Giuseppe Annoni, Andrea Borghini, Alessio Peretti, Marco Papa, Lamia Ait-Ali, Marie-Odile Bernier, Estelle Rage, Jérémie Dabin, Isabelle Thierry-Chef, Siamak Haghdoost, Eugenio Picano, Maria Grazia Andreassi","doi":"10.1093/carcin/bgag032","DOIUrl":"10.1093/carcin/bgag032","url":null,"abstract":"<p><p>The risk of cancer from medical exposure to ionizing radiation (IR) in pediatric patients-particularly those with congenital heart disease (CHD)-is a concern, given the need for repeated X-ray-guided cardiac catheterization (CC) procedures throughout their lives. To better understand the effects of low-dose IR, this study-part of the European HARMONIC project-investigated changes in blood miRNA expression following CC in CHD patients. Small RNA sequencing was performed on a discovery cohort of 10 CHD patients at three time points: before CC (T0), immediately after (T1), and 1 year later (T2). Differentially expressed miRNAs were validated in an independent group of 15 patients using quantitative real-time polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes pathway annotation analysis was carried out to determine the biological pathways involving target genes regulated by the dysregulated miRNAs. At the discovery stage, 74 miRNAs were significantly differentially expressed between the T1 and T0 groups, 69 between the T2 and T0 groups, and 41 between the T2 and T1 groups (q-value < 0.05 and |log2(fold change)|>1). Sixteen miRNAs (9 upregulated and 7 downregulated) were found to be dysregulated in both T1 and T2 compared to T0. Additionally, seven known miRNAs were uniquely dysregulated at T2. qRT-PCR analysis of six selected miRNAs partially validated the sequencing results, confirming consistent expression patterns for four miRNAs across cohorts. Pathway enrichment analysis indicated that predicted miRNA target genes were overrepresented in several pathways, including those annotated as cancer-related (enrichment P < .0001). These findings suggest potential associations with radiation exposure, but their biological significance and health implications remain uncertain and require further investigation.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}