International Journal of Cancer最新文献

{"title":"Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.","authors":"Florian Perner, Jayant Y Gadrey, Scott A Armstrong, Michael W M Kühn","doi":"10.1002/ijc.35332","DOIUrl":"https://doi.org/10.1002/ijc.35332","url":null,"abstract":"<p><p>Chromosomal rearrangements involving the Mixed Lineage Leukemia gene (MLL1, KMT2A) are defining a genetically distinct subset in about 10% of human acute leukemias. Translocations involving the KMT2A-locus at chromosome 11q23 are resulting in the formation of a chimeric oncogene, where the N-terminal part of KMT2A is fused to a variety of translocation partners. The most frequently found fusion partners of KMT2A in acute leukemia are the C-terminal parts of AFF1, MLLT3, MLLT1 and MLLT10. Unfortunately, the presence of an KMT2A-rearrangements is associated with adverse outcomes in leukemia patients. Moreover, non-rearranged KMT2A-complexes have been demonstrated to be crucial for disease development and maintenance in NPM1-mutated and NUP98-rearranged leukemia, expanding the spectrum of genetic disease subtypes that are dependent on KMT2A. Recent advances in the development of targeted therapy strategies to disrupt the function of KMT2A-complexes in leukemia have led to the establishment of Menin-KMT2A interaction inhibitors that effectively eradicate leukemia in preclinical model systems and show favorable tolerability and significant efficacy in early-phase clinical trials. Indeed, one Menin inhibitor, Revumenib, was recently approved for the treatment of patients with relapsed or refractory KMT2A-rearranged acute leukemia. However, single agent therapy can lead to resistance. In this Review article we summarize our current understanding about the biology of pathogenic KMT2A-complex function in cancer, specifically leukemia, and give a systematic overview of lessons learned from recent clinical and preclinical studies using Menin inhibitors.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062343","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":"Evidence for the atavistic reversal to a unicellular-like state as a central hallmark of cancer.","authors":"Joao Carvalho","doi":"10.1002/ijc.35355","DOIUrl":"https://doi.org/10.1002/ijc.35355","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062267","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":"Stage-specific characterization of \"early-onset colorectal cancer\": Localized and synchronous metastatic disease.","authors":"Erman Akkus, Beliz Bahar Karaoğlan, Mehmet Kayaalp, Utkucan Turmuş, Cihangir Akyol, Güngör Utkan","doi":"10.1002/ijc.35336","DOIUrl":"https://doi.org/10.1002/ijc.35336","url":null,"abstract":"<p><p>Early-onset colorectal cancer (EOCRC) is an alarming entity worldwide. Yet, stage-specific characteristics and prognosis in localized and synchronous metastatic EOCRC are not well-defined. Two cohorts of CRC patients (localized and synchronous metastatic) were evaluated, defining EOCRC as the diagnosis <50 years old. Five hundred sixty-eight patients were included (n = 432 localized, 14.4% [n = 62] EOCRC and n = 136 synchronous metastatic, 20.6% [n = 28] EOCRC). 93.5% of localized and 96.5% of synchronous metastatic EOCRC patients were symptomatic at diagnosis. Among localized patients, female gender (58.1% vs. 40%, p = .008), perineural invasion (41.9% vs. 24.9%, p = .005), folinic acid, 5-fluorouracil, and oxaliplatin chemotherapy (45.2% vs. 25.2%, p = .003), and perioperative chemotherapy cycles (9.21 [± 3.10] vs. 7.98 [± 2.92], p = .006) were higher in EOCRC compared with ≥50-year. Median recurrence-free survival (RFS) and overall survival were not reached in either group (p = .234 and p = .831). Only RAS mutant status was associated with RFS (Hazard ratio: 7.09 [95% confidence interval (CI): 1.87-26.76], p < .001) in EOCRC. Among synchronous metastatic patients, urgent surgery (32.1% vs. 11.1%, p = .014) and local treatments (39.3% vs. 20.4%, p = .037) were more frequent in EOCRC. Median progression-free survival and overall survival in the EOCRC and ≥50 years were 8.07 months (95% CI: 5.03-12.97) vs. 10.03 months (95% CI, 8.40-13.10) (p = .450) and 18.57 months (95% CI, 13.33-43.03) vs. 19.83 months (95% CI, 16.07-27.30) (p = .833), respectively. Synchronous metastatic EOCRC more frequently underwent urgent surgery (32.1% vs. 8%, p = .008) and had RAS mutation (43.5% vs. 16.7%, p = .032) than localized EOCRC. This study suggests that localized and synchronous metastatic EOCRC patients may have different characteristics than average onset, without survival differences. Implementation of stage-specific characteristics into daily practice is necessary for decision-making processes in these young patients.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062339","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":"\"Cell dedifferentiation\" versus \"evolutionary reversal\" theories of cancer: The direct contest of transcriptomic features.","authors":"Alexander E Vinogradov, Olga V Anatskaya","doi":"10.1002/ijc.35352","DOIUrl":"https://doi.org/10.1002/ijc.35352","url":null,"abstract":"<p><p>Cell dedifferentiation is considered an important hallmark of cancer. The atavistic reversal to a unicellular-like (UC) state is a less widely accepted concept, so far not included in the conventional hallmarks. The activated expression of ontogenetically earlier and evolutionary earlier genes in cancers supports both theories because ontogenesis partially recapitulates phylogenesis during cell differentiation (the cellular biogenetic law). We directly contested both types of gene signatures in stem vs. differentiated and cancer vs. normal cells, using meta-analysis of human single-cell transcriptomes (totally, 38 pairwise comparisons involving over 18,600 cells). Because compared cells can differ in proliferation rate, the correction for cell cycle activity was applied. Taken together as multiple variables in stem vs. differentiated cells analyses, the ontogenetic signature excluded the UC signature from predictive variables, usually even forcing it to change the sign of prediction (from plus to minus). In contrast, in cancer vs. normal cells, the UC signature excluded the ontogenetic signature. Thus, the direct contest decided in favor of the atavistic theory and placed a UC-like state as a central hallmark of cancer, which has a plausible evolutionarily formed mechanism (UC attractor) and can generate other hallmarks. These data suggest a paradigm shift in the understanding of oncogenesis and propose an integrative framework for cancer research. In a practical sense, the upregulation of UC signature over ontogenetic signature indicates potential tumorigenicity, which can be used in early diagnostics and regenerative medicine. For therapy, these results suggest the UC center of cellular networks as a universal target.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062243","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":"Beta-blockers and epithelial ovarian cancer survival: A Norwegian population-based cohort study.","authors":"Leif Lukas Löfling, Nathalie C Støer, Erica K Sloan, Sara Nafisi, Renée Turzanski Fortner, Edoardo Botteri","doi":"10.1002/ijc.35348","DOIUrl":"https://doi.org/10.1002/ijc.35348","url":null,"abstract":"<p><p>Cancer diagnosis and therapy cause stress to the body. Preclinical studies have shown that stress hormones can stimulate tumor progression and metastasis by interacting with β-adrenergic receptors, and that β-blockers can inhibit those processes. We assessed if β-blocker use was associated with survival in a nationwide cohort of women with epithelial ovarian cancer (EOC). We identified all women aged ≥40 years who underwent EOC surgery in 2004-2018 in Norway through the Cancer Registry of Norway. We estimated the association between peri-diagnostic and post-diagnostic β-blocker use and survival. We used Cox models, adjusted for sociodemographic and health factors, and reported hazard ratios (HRs) and 95% confidence intervals (CIs). The difference in overall survival time between β-blocker users and non-users was estimated as the difference in restricted mean survival time at 5 years after diagnosis using flexible parametric models. We included 3911 women with EOC; 540 (14%) used β-blockers at diagnosis, 1672 (43%) died of the disease, and 1882 (48%) died overall. We found an association between peri-diagnostic β-blocker use and longer EOC-specific survival (HR = 0.85, 95%CI 0.73-1.00; p-value = 0.048), and an indication of an association with overall survival (HR = 0.89, 95%CI 0.77-1.02; p-value = 0.101). Analysis of post-diagnostic β-blocker use, which included only women who survived 12 months or longer (n = 3344), found similar associations. At 5 years from diagnosis, peri-diagnostic β-blocker users lived on average 1.28 months longer than non-users (95%CI 0.01-2.60 months). The results support the hypothesis that β-blocker use improves EOC-specific survival in women with EOC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045130","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":"Mechanisms of enhancer-driven oncogene activation.","authors":"Joyce Vriend, Ruud Delwel, Dorien Pastoors","doi":"10.1002/ijc.35330","DOIUrl":"https://doi.org/10.1002/ijc.35330","url":null,"abstract":"<p><p>An aggressive subtype of acute myeloid leukemia (AML) is caused by enhancer hijacking resulting in MECOM overexpression. Several chromosomal rearrangements can lead to this: the most common (inv(3)/t(3;3)) results in a hijacked GATA2 enhancer, and there are several atypical MECOM rearrangements involving enhancers from other hematopoietic genes. The set of enhancers which can be hijacked by MECOM can also be hijacked by BCL11B. Enhancer deregulation is also a driver of oncogenesis in a range of other malignancies. The mechanisms of enhancer deregulation observed in other cancer types, including TAD boundary disruptions and the creation of de novo (super-) enhancers, may explain overexpression of MECOM or other oncogenes in AML without enhancer hijacking upon translocation. Gaining mechanistic insight in both enhancer deregulation and super-enhancer activity is critical to pave the way for new treatments for AML and other cancers that are the result of enhancer deregulation.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031755","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":"Socio-economic inequalities in second primary cancer incidence: A competing risks analysis of women with breast cancer in England between 2000 and 2018.","authors":"Ruchika Golani, Eva Kagenaar, Jérémie Jégu, Aurélien Belot, Suping Ling","doi":"10.1002/ijc.35320","DOIUrl":"https://doi.org/10.1002/ijc.35320","url":null,"abstract":"<p><p>We aimed to investigate socio-economic inequalities in second primary cancer (SPC) incidence among breast cancer survivors. Using Data from cancer registries in England, we included all women diagnosed with a first primary breast cancer (PBC) between 2000 and 2018 and aged between 18 and 99 years and followed them up from 6 months after the PBC diagnosis until a SPC event, death, or right censoring, whichever came first. We used flexible parametric survival models adjusting for age and year of PBC diagnosis, ethnicity, PBC tumour stage, comorbidity, and PBC treatments to model the cause-specific hazards of SPC incidence and death according to income deprivation, and then estimated standardised cumulative incidences of SPC by deprivation, taking death as the competing event. Multiple imputation was performed to account for missing data. Among 649,905 included women, 47,399 SPCs and 171,223 deaths occurred during 4,269,042 person-years of follow-up. Income deprivation was consistently associated with an increased rate of SPC incidence (cause-specific hazard ratio for the most vs. least deprived quintile: 1.29; 95% CI: 1.25, 1.33) and of death (1.36; 1.34, 1.38), translating into an absolute risk difference (the most vs. least deprived quintile) of 1.3% (95% CI: 1.0, 1.5) for SPC incidence and 4.9% (95% CI: 4.6, 5.1) for death at 10 years. Women with PBC from deprived areas in England faced a substantially higher risk of SPC than their counterparts. Future research is warranted to understand mechanisms for observed inequalities to inform strategies to monitor, prevent, and identify SPC in women with PBC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035475","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":"Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.","authors":"Kira Furlano, Tina Keshavarzian, Nadine Biernath, Annika Fendler, Maria de Santis, Joachim Weischenfeldt, Mathieu Lupien","doi":"10.1002/ijc.35327","DOIUrl":"https://doi.org/10.1002/ijc.35327","url":null,"abstract":"<p><p>Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases. As cellular plasticity is largely driven by non-genetic events, complementary studies in cancer epigenomics are now being conducted to identify chromatin variants. These variants, defined as genomic loci in cancer cells that show changes in chromatin state due to the loss or gain of epigenomic marks, inclusive of histone post-translational modifications, DNA methylation and histone variants, are considered the fundamental units of epigenomic heterogeneity. In prostate cancer chromatin variants hold the promise of guiding the new era of precision oncology. In this review, we explore the role of epigenomic heterogeneity in prostate cancer, focusing on how chromatin variants contribute to tumor evolution and therapy resistance. We therefore discuss their impact on cellular plasticity and stochastic events, highlighting the value of single-cell sequencing and liquid biopsy epigenomic assays to uncover new therapeutic targets and biomarkers. Ultimately, this review aims to support a new era of precision oncology, utilizing insights from epigenomics to improve prostate cancer patient outcomes.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031749","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":"Cervical cancer incidence rates considering migration status in mainland China using Bayesian model-Estimation based on 2016 cancer registry data.","authors":"Linlin Du, Huixin Sun, Liping Tang, Shuxiu Hao, Chen Feng, Guijin Li, Yu Zhang, Hong Jin, Cunqi Lv, Qingyu Zeng, Cheng Wang, Jiacheng Li, Xinshu Wang, Rong Ma, Tong Wang, Qi Li","doi":"10.1002/ijc.35346","DOIUrl":"https://doi.org/10.1002/ijc.35346","url":null,"abstract":"<p><p>In mainland China, cancer registration relies on household-registered populations, overlooking migrant populations. Estimating cervical cancer incidence among permanent residents, including migrants, offers a more accurate representation of the true burden. The data from 487 cancer registries across China in 2016 were analyzed using a Bayesian spatial regression model with the integrated nested Laplace approximation-stochastic partial differential equation method. The study estimated cervical cancer incidence among household-registered populations and adjusted for migrant populations using a weighting method based on interprovincial distribution and age stratification to derive the incidence of cervical cancer in the permanent residents. Data from the China Population Census, the China Migrants Dynamic Survey, and the Urban Statistical Yearbook were incorporated. The estimated crude incidence rate of cervical cancer among permanent residents was 17.4/100,000 in mainland China, with an age-standardized incidence rate (ASIR) of 17.2/100,000. The largest disparities in cervical cancer crude incidence rate between permanent residents and household-registered populations were observed in Guizhou (2.4/100,000, 95% CI 1.9-2.9/100,000), Zhejiang (-1.2/100,000, 95% CI -1.8 to -0.6/100,000) and Tianjin (-1.1/100,000, 95% CI -1.5 to -0.7/100,000). The number of the estimated cervical cancer incident cases was 8948. Guangdong saw an increase of 887 cases, while Henan had a decrease of 1430 cases. Guizhou had the highest ASIR (28.1/100,000), and Beijing had the lowest ASIR (11.0/100,000). The significance of this study is that it improves the accuracy of cervical cancer data in China. These findings provide evidence for developing cervical cancer prevention and control strategies, and offer insights for other countries and regions facing migration challenges.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031727","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 \"Impact of era of diagnosis on cause-specific late mortality among 77 423 five-year European survivors of childhood and adolescent cancer: The PanCareSurFup consortium\".","authors":"","doi":"10.1002/ijc.35284","DOIUrl":"https://doi.org/10.1002/ijc.35284","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031733","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}