Pellegrino RA, Shepherd BE, Pujari S
… +30 more, Fink V, Murenzi G, Nakalembe M, Coburn SB, Rohner E, Jaquet A, Lade C, Crabtree Ramirez B, Anastos K, Semeere A, Park LS, Mokone L, Boni S, Somia IKA, Jalil EM, Adedimeji A, Orang'o O, Silverberg MJ, Quarter KP, Messou E, Ross J, Gotuzzo E, Lelo P, Byakwaga H, Ezechi O, Euvrard J, Maruri F, Achenbach CJ, Castilho JL, International epidemiology Databases to Evaluate AIDS (IeDEA)
Int J Cancer
· 2026 Apr · PMID 41992467
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Cancer remains a leading cause of morbidity and mortality in people with HIV, and the importance of cancer screening increases as this population ages. In 2017, 2020, and 2023, cross-sectional surveys were conducted at H...Cancer remains a leading cause of morbidity and mortality in people with HIV, and the importance of cancer screening increases as this population ages. In 2017, 2020, and 2023, cross-sectional surveys were conducted at HIV care sites across 5 continents within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We described cancer screening availability in 2023 and over time for cervical and anal cancer screening using generalized estimating equations with a logit link function to account for site clustering, rurality, and country income. Of the 220 sites in the 2023 survey, 61% (134/220) reported cervical cancer screening by cytology or human papillomavirus (HPV) testing on-site, and 88% (194/220) reported cervical cancer screening by any method, including visual inspection. At sites serving predominantly rural populations, 62% (29/47) exclusively performed screening by visual inspection. Overall, 23% (50/220) of sites performed cytology-based anal cancer screening on-site, and 16% (35/220) had availability of high-resolution anoscopy, either on-site or by referral. Screening for cancer of the liver, colon, lung, prostate, or breast (by imaging) were each available at less than 43% of sites. The odds of cervical cancer screening availability increased by 16% annually from 2017 through 2023 (aOR = 1.16, 95% CI: 1.07-1.27, p = 0.001), while the relative odds of anal cancer screening availability decreased by 9% annually (aOR = 0.91, 95% CI: 0.84-0.99, p = 0.023). Lack of trained staff was the most frequently reported barrier, followed by lack of equipment. Understanding current practices and capacity is essential for the continued integration of cancer prevention in HIV care.
Ziel-Swier LJYM, Rassek K, Liu Y
… +10 more, Seitz A, Koerts J, de Jong D, Rutgers B, Kompaniiets A, Przybył J, Chamuleau MED, van den Berg A, Dzikiewicz-Krawczyk A, Kluiver J
Int J Cancer
· 2026 Apr · PMID 41992423
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We previously showed that ZDHHC11 promotes cell growth in Burkitt lymphoma (BL). To explore the underlying mechanism, we performed a genome-wide gene expression analysis upon ZDHHC11 knockdown. We identified MEF2B, a tra...We previously showed that ZDHHC11 promotes cell growth in Burkitt lymphoma (BL). To explore the underlying mechanism, we performed a genome-wide gene expression analysis upon ZDHHC11 knockdown. We identified MEF2B, a transcription factor critical for germinal center formation, as a downstream target and validated repression of MEF2B at the RNA and protein level upon ZDHHC11 knockdown in BL cell lines. The relevance of MEF2B was shown upon its knockdown, which strongly inhibited growth of BL cells. Since MEF2B is a known regulator of BCL6 in normal GC B-cells, diffuse large B-cell lymphoma, and follicular lymphoma, we subsequently focused on the effect of MEF2B knockdown on BCL6. We observed a strong decrease in BCL6 at the RNA and protein level in BL and showed a strong correlation between MEF2B and BCL6 transcript levels in a panel of B-cell lymphoma cell lines, primary BL samples, and normal B-cell subsets. Knockdown of BCL6 also strongly inhibited growth of BL cell lines, whereas BCL6 overexpression partially rescued the growth-inhibitory effect of MEF2B knockdown. Together, our data indicate that ZDHHC11 promotes BL cell growth at least in part by stimulating expression of MEF2B, which promoted BL cell survival through both BCL6-dependent and independent pathways. Our work highlighted the importance of the MEF2B-BCL6 axis, which strongly supports BL growth and identified ZDHHC11 as a novel regulator of this axis.
Sun Y, Liu X, Zhu Q
… +3 more, Sun Z, Wang C, Yan W
Int J Cancer
· 2026 Apr · PMID 41983866
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Synovial sarcoma (SS) is a rare and aggressive soft tissue sarcoma frequently associated with lung metastases. While anthracycline plus ifosfamide (AI) remains a standard first-line regimen, its benefit in SS patients wi...Synovial sarcoma (SS) is a rare and aggressive soft tissue sarcoma frequently associated with lung metastases. While anthracycline plus ifosfamide (AI) remains a standard first-line regimen, its benefit in SS patients with lung metastases is unknown. Anlotinib, a multi-target tyrosine kinase inhibitor (TKI), has shown promising effects in sarcoma treatment, but its combination with AI has not been well studied in this setting. This retrospective, single-center study included 108 SS patients with lung metastases treated between 2007 and 2024, receiving either AI alone (n = 59) or AI combined with anlotinib (n = 49). Survival outcomes were assessed using Kaplan-Meier analysis, and adverse events (AEs) were reviewed from clinical records. The results indicated that the combination therapy demonstrated statistically significant improvements in clinical outcomes compared to AI monotherapy, with a median PFS of 8.1 months versus 6.2 months (p = 0.0250), and a median OS of 14.8 months versus 6.8 months (p = 0.0033). Most AEs were Grades 1-2 according to common terminology criteria for adverse events (CTCAE) criteria, with manageable toxicity profiles. The combination group exhibited modest but clinically insignificant elevations in hypertension and proteinuria, with no reported treatment-related mortality. In conclusion, the anlotinib and AI chemotherapy combination regimen shows promising efficacy in prolonging survival duration for SS patients with lung metastases while maintaining an acceptable safety profile. These findings suggest that this combination therapy could be considered as a viable first-line treatment option for this patient population, warranting further validation through phase III randomized controlled trials.
Pellikka I, Ventelä J, Auvinen A
… +2 more, Lohi O, Nikkilä A
Int J Cancer
· 2026 Apr · PMID 41981796
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Emerging evidence indicates a possible association between acute leukemia and type 1 diabetes mellitus (T1DM). However, the relationship between acute leukemia and other autoimmune diseases (AIDs) remains less well under...Emerging evidence indicates a possible association between acute leukemia and type 1 diabetes mellitus (T1DM). However, the relationship between acute leukemia and other autoimmune diseases (AIDs) remains less well understood. To address this gap, we conducted a case-control study using detailed Finnish register-based data. We identified 1626 childhood leukemia cases (diagnosed 1990-2019) from the Finnish Cancer Registry and sampled three age- and sex-matched controls per case. Information on 29 AIDs, based on previous literature, was obtained from the Care Register of the Finnish Institute for Health and Welfare and on T1DM from the Social Insurance Institution of Finland. Subjects with Down syndrome were excluded. Conditional logistic regression, adjusted for maternal smoking and large for gestational age, was used to estimate associations. After excluding T1DM, AIDs remained associated with an increased risk of childhood leukemia (OR 1.8, 95% CI 1.4-2.4), the association primarily driven by acute lymphoblastic leukemia (OR 1.9, 95% CI 1.4-2.6). Of the AIDs, the association was strongest with rheumatoid diseases (OR 2.6, 95% CI 1.3-4.9). Using lag periods to account for potential sources of bias did not materially change the results. Childhood leukemia, particularly acute lymphoblastic leukemia, was associated with a higher prevalence of AID, independent of T1DM. The findings warrant further investigation on potential shared immune dysregulation or environmental triggers.
Int J Cancer
· 2026 Aug · PMID 41972846
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Hypoxia is an important cause of radiotherapy resistance in head and neck cancers. Cancer cells adapt to hypoxic conditions through various molecular alterations, leading to treatment resistance and tumor progression. A...Hypoxia is an important cause of radiotherapy resistance in head and neck cancers. Cancer cells adapt to hypoxic conditions through various molecular alterations, leading to treatment resistance and tumor progression. A deeper understanding of these hypoxia-induced molecular alterations is essential for future development of effective hypoxia targeting and radiosensitizing therapies. In this study, we tracked (post-)hypoxic cells at single-cell level in HPV-negative and HPV-positive HNSCC models using a hypoxia fate mapping system. We found that (post-)hypoxic cells drive regrowth after radiotherapy in 3D conditions and showed an increased resistance to radiation. Transcriptomic analysis showed that post-hypoxic cells are characterized by a gene expression signature mainly defined by checkpoint regulation. Consistent with these findings, radiotherapy resistant post-hypoxic cells showed a reduced number of radiotherapy-induced micronuclei and mitotic spindle aberrations, indicating a mitotic survival advantage. Inhibition of mitotic checkpoint proteins ATR and CHK1/2 increased the radiosensitivity of post-hypoxic cells. In conclusion, our findings indicate that radiotherapy resistance in HNSCC cells is associated with mitotic survival advantage of post-hypoxic cells, independent of HPV-status.
Malcomson L, Brentnall A, Renehan AG
… +5 more, Pegington M, Harkness EF, Southworth J, Evans DG, Harvie M
Int J Cancer
· 2026 Apr · PMID 41968390
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Adult weight gain (AWG) increases postmenopausal breast cancer risk, whereas an early first pregnancy (FP) is protective. As pregnancy is a key contributor to weight gain, we investigated a potential interaction effect b...Adult weight gain (AWG) increases postmenopausal breast cancer risk, whereas an early first pregnancy (FP) is protective. As pregnancy is a key contributor to weight gain, we investigated a potential interaction effect between these two factors on BC risk. We analysed prospective data from 48,417 women in the Predicting Risk of Breast Cancer at Screening (PROCAS) cohort (recruited 2009-2015). A Cox proportional hazards model was used to test for an interaction between first pregnancy age and weight gain on breast cancer risk. After a median follow-up of 6.4 years, 1702 incident breast cancers were identified. Compared to women with an early FP (< 30 years) and stable weight (≤ 5%), risk was highest among those with substantial AWG (> 30%) combined with a late FP (≥ 30 years) (HR: 2.48, 95% CI: 1.82-3.37) or nulliparity (HR: 2.38, 95% CI: 1.74-3.27). Elevated risk was observed even with moderate weight gain (5%-15%). A non-significant positive trend toward an additive interaction was observed for late FP (Relative Excess Risk due to Interaction (RERI): 0.32), whereas the risk in nulliparous women appeared independent of weight gain (RERI: -0.05). Maintaining a stable adult weight and an early first pregnancy are independently associated with a lower breast cancer risk. However, adult weight gain remains a significant risk factor regardless of reproductive history. The combination of high weight gain and late or no pregnancy identifies a high-risk group who could be prioritized for weight-management interventions in cancer prevention settings.
Andour L, Hagenaars SC, de Groot AF
… +6 more, Krol-Warmerdam EMM, Kroep JR, Hazelbag HM, Liefers GJ, Straver ME, Mesker WE
Int J Cancer
· 2026 Aug · PMID 41964157
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Approximately 75% of breast cancers are hormone receptor-positive (HR+). Endocrine therapy may be administered to improve survival. Neoadjuvant therapy may enable breast- and axilla-conserving surgery, but identifying wh...Approximately 75% of breast cancers are hormone receptor-positive (HR+). Endocrine therapy may be administered to improve survival. Neoadjuvant therapy may enable breast- and axilla-conserving surgery, but identifying who will benefit remains challenging. This study evaluates the predictive value of the tumor-stroma ratio (TSR) for response to neoadjuvant endocrine therapy (NET) and examines the accuracy of MRI in predicting (near) pathological complete response (pCR). Women diagnosed between 2014 and 2024 with invasive HR+, human epidermal growth factor 2-negative breast cancer who received NET in two Dutch hospitals were included. A total of 208 women (215 tumors) were included, of whom 81 (37.7%) had a stroma-low tumor and 134 (62.3%) stroma-high. Almost 1 out of 4 stroma-low cases achieved (near) pCR after NET. In both univariable (OR 2.85, 95% CI 1.32-6.15, p = 0.008) and multivariable analysis (OR 3.70, 95% CI 1.54-8.90, p = 0.003), stroma-low tumors showed an increased likelihood of achieving (near) pCR compared to stroma-high tumors. In node-positive patients (n = 117), univariable analysis presented higher odds of pCR in the axilla after NET in the stroma-low group (OR 4.41, 95% CI 1.08-18.08, p = 0.039), although this was not significant in multivariable analysis (p = 0.060). The MRI correctly reported (near) pCR in 12 (75%) stroma-low cases and 8 (35%) stroma-high. Stroma-low patients significantly more often achieved (near) pCR of the tumor and axilla after NET compared to stroma-high patients. The accuracy of MRI to predict (near) pCR was higher in the stroma-low group compared to the stroma-high group.
Beaussire-Trouvay L, Obongo-Anga FR, Lévêque E
… +13 more, Berghian A, François A, Bon-Mardion N, Meret E, Deneuve S, Bohers E, Viennot M, Burel L, Libraire J, Libert L, Sarafan-Vasseur N, Di Fiore F, Clatot F
Int J Cancer
· 2026 Aug · PMID 41964148
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ctDNA is a promising tool to optimize therapeutic strategies in patients treated for locally advanced head and neck cancer that is negative for Human Papilloma Virus (LAHNSCC/HPV-). The objective was to evaluate pre and...ctDNA is a promising tool to optimize therapeutic strategies in patients treated for locally advanced head and neck cancer that is negative for Human Papilloma Virus (LAHNSCC/HPV-). The objective was to evaluate pre and postoperative detection of circulating tumor DNA (ctDNA) using a customized Next-Generation Sequencing (NGS) tumor-informed assay. We conducted a prospective study including patients treated with initial surgery for a LAHNSCC/HPV-. We developed an NGS assay covering the exons of 11 genes for tumor and ctDNA analysis. DNA alterations were interpreted according to two classes of variants: "pathogenic variants" classified as class 4 or 5 in public databases and "tumor specific variants" corresponding to alterations detected exclusively in tumor DNA after paired analysis of normal cell DNA using the same NGS panel. A total of 40 patients were included, 45% with T4 and 62.5% with N+ disease. Regarding tumor profiles, 41 "pathogenic variants" were detected corresponding to 30/36 (83.3%) of informative tumors with at least one alteration. In contrast, 354 "tumor specific variants" were identified with at least one alteration in 35/35 (100%) informative tumors. For ctDNA, the NGS panel was associated with a positivity rate of 74.3% and 37.1% pre and postoperative, respectively, using tumor specific variants; compared with 20% and 2.5% using interpretation of pathogenic variant. Pretreatment ctDNA positivity according to pathogenic variant was associated with lower specific progression-free survival (p = 0.025). Our customized 11-genes NGS panel tumor-informed assay provides high rates of ctDNA detection and may be used to evaluate new strategies in LA HNSCC/HPV- patients.
Gendrau-Sanclemente N, Figueras A, Medina-Jover F
… +10 more, Marín-Jiménez JA, De Leeuw M, Dai T, Moreno-Mosquera M, Morales A, Guiu M, Casas J, Perales JC, Gomis RR, Viñals F
Int J Cancer
· 2026 Aug · PMID 41958014
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Despite extensive clinical endeavors to enhance high-grade serous ovarian cancer (HGSOC) detection and treatment, an alarming half of diagnosed women succumb annually to this disease. Significantly, nearly all HGSOC case...Despite extensive clinical endeavors to enhance high-grade serous ovarian cancer (HGSOC) detection and treatment, an alarming half of diagnosed women succumb annually to this disease. Significantly, nearly all HGSOC cases manifest ascites at diagnosis, a poor prognostic indicator. Malignant ascites production arises as ovarian cancer cells shed from the primary tumor, creating a new environment that challenges their survival. Consequently, cancer cells aggregate into tumorspheres, the principal metastatic units in HGSOC. The molecular mechanisms that tumorspheres use to overcome the ascites bottleneck and metastasize are still poorly understood. Studying tumorspheres isolated from ascites samples from treatment naïve HGSOC patients, as well as three-dimensional spheroid in vitro and in vivo ovarian cancer cell models, we report that the sphingosine-1-phosphate (S1P) ligand and its receptor S1PR1 axis is especially relevant in ovarian tumorspheres, where it promotes an autocrine positive loop, serving as their primary proliferative mechanism via MEK1/2-ERK activation. Our findings demonstrate that the S1P-S1PR1-MEK1/2 pathway confers ovarian tumorspheres a selective advantage within the ascites environment and, consequently, increases their metastatic potential.
Wang J, Song P, Ge Y
… +10 more, Yang H, Li S, Ma R, Ma T, Feng S, Zhang C, Sun T, Yao F, Yi J, Zhang H
Int J Cancer
· 2026 Aug · PMID 41957998
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Radical surgery following neoadjuvant immunochemotherapy (NICT) has emerged as a critical therapeutic strategy in the standardized management of locally advanced non-small cell lung cancer (NSCLC). Robust evidence on the...Radical surgery following neoadjuvant immunochemotherapy (NICT) has emerged as a critical therapeutic strategy in the standardized management of locally advanced non-small cell lung cancer (NSCLC). Robust evidence on the optimal time interval between NICT and surgery is lacking. Patients were divided into three groups based on the interval between the completion of NICT and surgery: short interval group (SIG; < 4 weeks), intermediate interval group (IIG; 4-6 weeks), and long interval group (LIG; > 6 weeks). Inverse probability treatment weighting (IPTW) and weighted regression analysis were used to balance the baseline characteristics and compare the outcomes. 205 out of 335 screened patients met the inclusion criteria and were enrolled. When compared with the IIG, the SIG (OR, 0.15; 95% CI, 0.06-0.38; p < 0.001) was significantly correlated with lower pCR rate and the DFS was worse in the LIG (HR, 2.35; 95% CI, 1.15-4.80; p = 0.019). Subgroup analysis revealed that, in patients with a poor tumor regression response, LIG was significantly associated with poorer DFS (HR, 5.15; 95% CI, 2.27-11.71; p < 0.001) and OS (HR, 4.52; 95% CI, 1.48-13.79; p = 0.008) when compared with the IIG. Similarly, in patients with non-pCR, LIG was significantly associated with poorer DFS (HR, 3.25; 95% CI, 1.39-7.61; p = 0.006) and OS (HR, 2.72; 95% CI, 1.00-7.38; p = 0.049). Surgery performed within 4-6 weeks after the completion of NICT is associated with improved pCR and DFS. Emphasis should be placed on early surgical treatment after NICT, particularly in patients who have poor or no response to NICT.
Šavrova A, Jakoby H, Tisler A
… +4 more, Innos K, Maiväli Ü, Jaal J, Uusküla A
Int J Cancer
· 2026 Aug · PMID 41957967
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Effective cervical cancer screening and progress toward WHO elimination targets depend on complete follow-up for women with positive primary screening tests. However, real-world data on this critical step in hrHPV-based...Effective cervical cancer screening and progress toward WHO elimination targets depend on complete follow-up for women with positive primary screening tests. However, real-world data on this critical step in hrHPV-based screening programs in Eastern Europe are scarce. We conducted a nationwide, population-based retrospective cohort study in Estonia, analyzing records from the Estonian Health Insurance Fund and Population Register. We included 44,282 women aged 30-65 who were invited to hrHPV-based screening between January 1, 2021, and December 31, 2022, with follow-up through March 31, 2024. Screening attendance was 45.7% (n = 20,242; 95% CI: 45.2%-46.2%), with 8.0% (n = 1615; 95% CI: 7.6%-8.4%) testing hrHPV-positive. A substantial loss to follow-up was observed: 57.7% of hrHPV-positive women did not undergo repeat hrHPV testing, colposcopy, or any post-colposcopy care within 12 months. Among those referred for further diagnosis, colposcopy was performed in 77.9% within 6 months. Treatment for High-Grade Squamous Intraepithelial Lesion (HSIL) cases was high (85.5%; n = 124; 95% CI: 78.7%-90.5%), mostly within 3 months. Predictors of lower follow-up adherence included older age and residence in South Estonia. Suboptimal screening uptake and high loss to follow-up among hrHPV-positive women are significant barriers to effective cervical cancer prevention in Estonia. These challenges mirror those seen in many organized screening programs globally. Prioritizing strategies to enhance follow-up adherence is critical for timely diagnosis and treatment, ultimately accelerating global efforts toward cervical cancer elimination.
Li X, Zhao Z, Stassen L
… +8 more, Maya AP, Bhardwaj M, Seum T, Raut JR, Gwenzi T, Hoffmeister M, Schrotz-King P, Brenner H
Int J Cancer
· 2026 Jul · PMID 41957956
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This study aimed to conduct a head-to-head comparison of the diagnostic value of serum carcinoembryonic antigen (sCEA) and fecal CEA (fCEA) for colorectal cancer (CRC) detection. Fecal and serum samples from 80 CRC cases...This study aimed to conduct a head-to-head comparison of the diagnostic value of serum carcinoembryonic antigen (sCEA) and fecal CEA (fCEA) for colorectal cancer (CRC) detection. Fecal and serum samples from 80 CRC cases at various tumor stages and 100 controls free of colorectal neoplasms at screening colonoscopy were randomly selected from two ongoing large prospective CRC detection studies (IDA and BLITZ) for CEA measurements. Fecal samples were processed using two methods: with and without mechanical homogenization. Diagnostic performance (area under the curve value [AUC], sensitivity) of fCEA and sCEA was compared individually and in combination with fecal immunochemical test (FIT). The fCEA concentrations obtained using both sample processing methods were highly correlated in both CRC cases and controls, but neither correlated with sCEA. The sCEA concentrations demonstrated significantly greater differences between the CRC and control group compared to fCEA concentrations. The diagnostic performance of fCEA obtained with both fecal sample processing methods was significantly lower than that of sCEA (AUC: 0.62 and 0.57 vs. 0.83, both p < .001; sensitivity at 85% specificity: 36.2% and 26.2% vs. 52.5%, p = .067 and .002). Algorithms combining sCEA with fCEA did not significantly improve the diagnostic performance compared to sCEA alone. Combining FIT with sCEA improved diagnostic performance over FIT alone. However, combining FIT with fCEA showed no improvement. In conclusion, fCEA is inferior to sCEA as a non-invasive biomarker for CRC detection. Combination of FIT with sCEA demonstrates greater potential for CRC screening than combination of FIT with fCEA.
Seum T, Mandic M, Safizadeh F
… +2 more, Hoffmeister M, Brenner H
Int J Cancer
· 2026 Aug · PMID 41957948
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The incidence of obesity and early-onset colorectal cancer (CRC) has rapidly increased in recent decades. We estimated CRC risk differences by body mass index (BMI) and derived corresponding BMI-specific CRC screening in...The incidence of obesity and early-onset colorectal cancer (CRC) has rapidly increased in recent decades. We estimated CRC risk differences by body mass index (BMI) and derived corresponding BMI-specific CRC screening initiation ages across multiple countries, to help refine the timing of CRC prevention. We based our analyses on population-level CRC incidence data from the GLOBOCAN database (2022) and risk estimates from a meta-analysis of six cohort studies. The analysis included adults aged 30 to 60 years from six countries: United States, Canada, Germany, France, United Kingdom, and Italy. Individuals with overweight were used as the reference category, reflecting the average BMI of adults eligible for screening in these countries. Risk-adapted screening initiation ages were defined as the ages at which individuals with obesity reached the same 5-year cumulative CRC risk as those with overweight at ages 45 and 50 (aCR and aCR). Compared with individuals with overweight, those with normal weight had a lower risk of early-onset CRC (OR, 0.76; 95% CI, 0.68-0.84), while those with obesity had higher risk (OR, 1.42; 95% CI, 1.04-1.95). Across countries, individuals with obesity reached the aCR at age 41 to 42 years and the aCR at age 46 to 47 years. These findings indicate that individuals with obesity reached CRC screening thresholds up to 3-4 years earlier than those at average risk. BMI may offer a practical and scalable marker to inform personalized CRC screening initiation, with the potential to enhance early detection if integrated into existing screening programs.
Int J Cancer
· 2026 Aug · PMID 41957941
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Glioblastomas (GBMs) are highly aggressive and therapy-resistant brain tumors, mainly driven by stem-like cells and profound metabolic plasticity. Novel treatment strategies, including mechanical high-intensity focused u...Glioblastomas (GBMs) are highly aggressive and therapy-resistant brain tumors, mainly driven by stem-like cells and profound metabolic plasticity. Novel treatment strategies, including mechanical high-intensity focused ultrasound (mFUS), are being developed, but their effects on tumor metabolism remain poorly understood. To address this gap, we investigated the impact of mFUS on carbohydrate metabolism in patient-derived GBM organoids and 3D glioma stem-like cell (GSC) cultures. We showed that mFUS selectively induced the expression of glycolysis- and metabolite-transport-associated molecules (GLUT1, HK2, PKM2, LDHA, MCT1, MCT4), particularly in GSCs, as confirmed by qPCR and immunofluorescence. Functional assays demonstrated increased glucose uptake after mFUS, while lactate production remained unchanged. Notably, pharmacological inhibition of GLUT1 or MCT1 potentiated the cytotoxic effects of mFUS, significantly reducing the survival of peri-focal GSCs. Together, these results reveal that mFUS promotes metabolic adaptations in GBM cells and that combined metabolic inhibition may enhance its therapeutic efficacy.
Sun Y, Dong L, Tan H
… +4 more, Zhao D, Zhao H, Ying J, Chi Y
Int J Cancer
· 2026 Aug · PMID 41954240
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Certain hereditary syndromes increase the incidence of neuroendocrine tumors (NETs), suggesting germline variation may play a role in NET pathogenesis. However, the germline mutation spectrum in Chinese NET patients rema...Certain hereditary syndromes increase the incidence of neuroendocrine tumors (NETs), suggesting germline variation may play a role in NET pathogenesis. However, the germline mutation spectrum in Chinese NET patients remains unclear. This study aimed to investigate the germline genetic variations and associated clinicopathological features in Chinese NET patients. A single-center retrospective study was conducted at the Cancer Hospital of Chinese Academy of Medical Sciences; 453 histologically confirmed NET patients who received germline genetic testing between June 2018 and March 2025 were enrolled. Germline DNA extracted from saliva or blood samples was analyzed using multigene panels and whole-exome sequencing. Results showed 11.5% (52/453) cases carried germline pathogenic or likely pathogenic variants (P/LPVs) across 28 cancer predisposing genes. MEN1 was the most frequently mutated gene, accounting for 3.5% (16/453) of all enrolled patients, followed by PALB2, SDHB, and BRIP1. The most common variant of uncertain significance (VUS) was found in MUTYH. Compared with non-carriers, P/LPV carriers were characterized by a significantly younger age at diagnosis (p < 0.001), male predominance (p = 0.008), higher tumor grade (p = 0.006), a stronger family history of cancer (p = 0.047), different primary tumor locations (p < 0.001), lower somatostatin receptor 2 expression (p = 0.010), and more aggressive tumor behavior, including higher metastatic rate (p = 0.002) and advanced stage (p = 0.011). Furthermore, patients with MEN1 P/LPVs had more mediastinal tumors and a younger age than those with non-MEN1 P/LPVs. This study, which is the largest to date regarding germline variations in Chinese patients with NETs, reveals a distinct mutational profile and identifies the unique clinicopathological features among carriers of germline P/LPVs.
Meng J, Ge L, Wang X
… +11 more, Yu Z, Cheng P, Yang M, Li J, Wu D, Zhou Y, Zhu J, Chen Z, Peng Y, Li Y, Zhao W
Int J Cancer
· 2026 Aug · PMID 41952618
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This study evaluated the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system in Chinese uterine serous carcinoma (USC) patients and defined the disease's molecul...This study evaluated the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system in Chinese uterine serous carcinoma (USC) patients and defined the disease's molecular landscape. Retrospective analysis classified USC patients by both 2009 and 2023 FIGO systems; staging migration was analyzed via cross-tabulation and Sankey diagrams. Molecular classification used the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) algorithm, with human epidermal growth factor receptor 2 (HER2) expression assessed by immunohistochemistry (IHC). Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and log-rank tests; the 2023 system's prognostic ability was validated via time-dependent receiver operating characteristic (ROC) curves, Harrell's C-index, and Akaike's Information Criterion (AIC). The 2023 system induced significant staging migration, mainly from IA/IB to IC (endometrium-confined tumors) or IIC (myometrial invasion). This reclassification achieved better prognostic stratification, shown by higher C-index and lower AIC than the 2009 system. Molecular profiling clarified subtype distribution, and HER2 overexpression was confirmed in substantial subsets, highlighting therapeutic relevance. The 2023 FIGO staging system provides superior prognostic stratification for Chinese USC patients compared to the 2009 version.
Wang CC, Paternostro F, Wozniak A
… +8 more, De Cock L, De Sutter L, Verbeeck K, Vanleeuw U, Gorgels D, Lee CJ, Sciot R, Schöffski P
Int J Cancer
· 2026 Aug · PMID 41952298
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Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. While imatinib and other tyrosine kinase inhibitors have improved the survival of patients with advanced GIST,...Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. While imatinib and other tyrosine kinase inhibitors have improved the survival of patients with advanced GIST, these treatments are not curative. Additionally, drug resistance eventually develops in most cases. Therefore, there is an unmet need to develop new therapeutic strategies for advanced GIST. This study is the first to comprehensively analyze the molecular epidemiology of urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180/CD280) expression in GIST, highlighting its potential as an attractive target for targeted therapy. We analyzed uPARAP expression in GIST samples using tissue microarrays (TMAs) constructed from clinically annotated patient samples and GIST xenograft specimens. Our results demonstrated that all clinical GIST samples were positive for uPARAP expression, with high expression found in 79% (52/66) of samples. There was no statistically significant correlation between uPARAP expression and relevant clinical parameters, including gender, sample status (primary tumor or metastatic lesion), clinical outcome, mutation status, primary tumor location, and risk class, indicating that uPARAP has no prognostic role in this setting. In xenograft GIST samples, high uPARAP expression was found in 53% (8/15) of models, with a homogeneous distribution of expression in the majority of the samples. This study emphasizes the potential of uPARAP as a druggable target and paves the way for further (pre)clinical evaluation of anti-uPARAP therapy in advanced GIST.
Koto R, Yamamoto A, Takashima I
… +5 more, Iwao C, Shin JH, Hayashi Y, Kitagawa H, Horie Y
Int J Cancer
· 2026 Aug · PMID 41952286
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Greater understanding of the prognosis for patients with lung cancer in Japan according to detection pathway would clarify the effect of population-based screening programs and the related diagnostic environment. We expl...Greater understanding of the prognosis for patients with lung cancer in Japan according to detection pathway would clarify the effect of population-based screening programs and the related diagnostic environment. We explored the clinical characteristics and net survival (NS) of patients with lung cancer by detection pathway with Japanese National Cancer Registry (NCR) database of patients registered between 2016 and 2020. Eligible patients were categorized based on detection pathway: Screening, Incidental, and Other groups. We estimated 1, 2, and 3 year NS. Of 565,044 patients with lung cancer in the NCR, 563,244 met the eligibility criteria and were included in this study: 95,081 patients in the Screening (16.9%), 254,569 in the Incidental (45.2%), and 200,850 in the Other groups (35.7%). In the Screening, Incidental, and Other groups, 69.5%, 88.6%, and 83.4% of patients, respectively, were aged ≥ 65 years, and 50.5%, 49.6%, and 14.0% of patients, respectively, had localized disease at diagnosis. The most common initial treatment was surgery in the Screening (62.5%) and Incidental (46.2%) groups, while chemotherapy was most frequently used in the Other group (48.6%). The 3 year NS was 75.2% (95% confidence interval: 74.9%-75.6%) in the Screening group, 56.3% (56.0%-56.6%) in the Incidental group, and 29.4% (29.2%-29.7%) in the Other group. In the subgroup analysis, 3 year NS for localized disease was 96.3% (95.9%-96.7%), 83.9% (83.6%-84.3%), and 76.9% (76.1%-77.6%), respectively, for the Screening, Incidental, and Other groups. Screening may play a key role in early detection and is likely to contribute to survival outcomes.
Hawwash NK, Sperrin M, Martin GP
… +11 more, Sinha R, Matthews CE, Schulze MB, Hiensch A, Amiano P, Neuhouser ML, Joshu CE, Platz EA, Freisling H, Gunter MJ, Renehan AG
Int J Cancer
· 2026 Aug · PMID 41952250
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At least 13 cancers are linked to obesity. We analyse time-to-event data using Sensitive Period Analysis to explore whether associations between body mass index (BMI) and cancer incidence vary throughout adulthood to inf...At least 13 cancers are linked to obesity. We analyse time-to-event data using Sensitive Period Analysis to explore whether associations between body mass index (BMI) and cancer incidence vary throughout adulthood to inform cancer prevention strategies, policy and weight management trials of optimal intervention ages. Using the European Prospective Investigation into Cancer and Nutrition cohort, Atherosclerosis Risk in Communities study, Women's Health Initiative, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial, NIH-AARP Diet and Health, we predicted BMI throughout adulthood. We landmarked to predefined ages of interest (AOI), ages 30 to 65 (5-yearly). Super-landmarking and a two-stage IPD meta-analysis were used. A single stratified Cox proportional hazards model with interaction terms between BMI and AOIs was fitted to analyse associations between per 5 kg/m BMI at AOIs and cancer incidence and identify sensitive age periods. 720,210 participants were followed up over 9.85 years in men and 10.80 years in women. Positive associations were found per 5 kg/m BMI across ages 30-65 for obesity-related cancers. Some evidence suggests BMI in the 40s-50s raises cancer risk more than baseline. Interactions by age were found in women at ages 35 and 40 for obesity-related cancers with HRs per 5 kg/m of 1.04 (95% CI: 1.01, 1.07, I :0%) and 1.05 (95% CI: 1.01, 1.09, I :50%), respectively, and at ages 35-65 for postmenopausal breast cancer. Higher BMI increased obesity-related cancer risk across ages 30-65. Similar associations across adulthood suggest adiposity at any age increases cancer risk. Policymakers should prevent excess adiposity accumulation in early life to minimise cancer risk.