International Journal of Cancer最新文献

Diffuse intrinsic pontine gliomas (DIPG) are highly aggressive brainstem tumors, representing the leading cause of pediatric cancer-related mortality despite their rarity. DIPGs are predominantly characterized by the H3K27M mutation, which drives tumorigenesis through epigenomic reprogramming and dysregulated gene expression. A major barrier to therapeutic advancement has been the scarcity of representative preclinical models, historically limited by the rarity of tumor tissue samples. Recent advancements in biopsy safety and model development have accelerated progress in understanding DIPG biology and developing novel therapies. While current murine models offer valuable insights, they often fail to replicate the tumor's genetic and microenvironmental complexity fully. Non-murine models offer cost-effective platforms but are limited by anatomical and immunological differences that reduce their relevance to human DIPG. This review highlights advances and limitations in DIPG models, emphasizing the need for integrative approaches using multiple systems to validate therapies, as no single model can fully capture the disease's complexity. Addressing these gaps could lead to the development of novel treatments for DIPG.

Several international guidelines consider sensitivity (of test, episode, or programme) and related measures of the detection of prevalent cases of target disease to be among key performance indicators for quality control of routine cancer screening programmes and use them to identify suboptimal providers. We aimed to describe the variability encountered in real-world settings around the measurement of these quantities in cervical and colorectal cancer screening, where the target for disease detection includes preinvasive disease. We performed a scoping review of grey literature, including international guidelines, annual statistical reports, and other official documents from European cervical and colorectal screening programmes. From the reviewed material, we extracted information on 20 measures used for this purpose. Some measures have been adopted in several programmes, but none have been used in all, not even within the same cancer type. While many of the methods might appear plausible for the intended use, our analysis showed that when applied to routinely collected data they may provide misleading or uninterpretable estimates of the ability of individual providers and the service as a whole to detect prevalent cases. Screening programmes should be cautious in their choice and interpretation of these measures. Further methodological development is required to better support policymakers and quality control managers in prioritising measures that are fit for purpose in routine cancer screening programmes.

Ipilimumab and nivolumab are recommended as first-line therapy for patients with metastatic or advanced renal cell carcinoma (aRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate or poor risk. We retrospectively evaluated efficacy and safety in a multi-center real-world cohort with 356 patients initiating ipilimumab and nivolumab from 17 centers in Germany and Switzerland. Median age was 64 years, most patients were male (69.1%) and had clear cell histology (74.1%). IMDC risk was intermediate in 61.8% and poor in 28.7%. About 37.1% of cases did not meet the inclusion criteria for the CheckMate 214 pivotal study (e.g., poor Eastern Cooperative Oncology Group [Performance Status Scale] [ECOG] status, comorbidities, brain metastases, and impaired renal function). After a median follow-up of 17.5 months, complete response was seen in 8.7%, partial response in 28.7% of patients. Median progression-free survival (PFS) was 8 (95% confidence interval [CI] 5.4-10.6) and median overall survival (OS) 39 months (95% CI 27.5-50.5). Subgroup analysis of patients with non-clear cell histology showed a shorter PFS and OS. Other negative predictors were poor ECOG, fewer induction cycles, ineligibility to pivotal study, and hepatic metastases. Adverse events occurred in 76.4% of patients (35.4% ≥ grade 3). High-dose corticosteroids were applied in 27.3% of cases. Cabozantinib was most frequently administered (63.4%) as subsequent therapy and showed superior OS and PFS compared to other second-line options. Our data support ipilimumab and nivolumab as a first-line treatment of aRCC with robust efficacy and safety. Patient selection was less restrictive in our clinical practice and may explain differences to CheckMate 214 trial.

Cooley V, Fortner RT, Mukama T, et al. Prospective evaluation of 92 protein biomarkers for early detection of endometrial cancer. Int J Cancer. 2025;157(3):480-489. doi:10.1002/ijc.35428

In the funding section, the text “The article is supported by the Dalgleish Centre for Myeloma and Related Blood Cancers and Leukemia and Lymphoma Society” was incorrect.

This should have read:

Funding: The author(s) received no specific funding for this work. The coordination of EPIC-Europe is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Nationale Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale (MGEN), Institut National de la Santé et de la Recherche Médicale (INSERM), French National Research Agency (ANR, reference ANR-10-COHO-0006), French Ministry for Higher Education (subsidy 2102918823, 2103236497, and 2103586016) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Italian Ministry of Health, Italian Ministry of University and Research (MUR), Compagnia di San Paolo (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Organisation for Health Research and Development (ZonMW), World Cancer Research Fund (WCRF) (the Netherlands); UiT, the Arctic University of Norway; Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1, MC-UU_12015/1, and MC_UU_00006/1 to EPIC-Norfolk; MR/Y013662/1 to EPIC-Oxford) (United Kingdom).

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Anti-estrogens have had a limited impact on breast cancer (BC) prevention. Novel agents with better tolerability, and efficacy beyond estrogen receptor (ER) positive BC are needed. We studied licochalcone A (LicA) for ER-agnostic BC prevention. We demonstrated that LicA significantly reduced proliferation in seven human breast cell lines and suppressed ER+ and ER- xenograft tumors in mice. We confirmed these observations ex vivo in the contralateral unaffected breast (CUB) of women with unilateral sporadic BC, and BC cell lines using RNA sequencing, metabolism flux modeling, confirmatory NanoString nCounter metabolic pathway panel analysis in independent sets of specimens, proteomics, and western blots. We found that LicA targets sterol regulatory element binding protein 1 (SREBP1) with subsequent metabolic-inflammatory changes, lowering spatiotemporally resolved cholesterol levels inside malignant cells to the levels in normal mammary cells. Mechanistically, in CUBs we observed that LicA downregulated PI3K-AKT-SREBP1-dependent lipogenesis, NF-kB-dependent inflammation, and de novo nucleotide biosynthesis, stalling proliferation. Studies in cell lines showed suppression of PI3K and AKT phosphorylation, SREBP1 protein expression, and the SREBP1-dependent enzymes such as ACAT2, ACLY, FASN, SCD, consistent with reduced NEDD8 required for SREBP1 stabilization. We found a significant reduction in NF-kB expression, its nuclear translocation mediator karyopherin β1, and prostaglandin E2 synthesis. We demonstrated a reduction in PRPS1-catalyzed de novo nucleotide biosynthesis, and downregulation of proliferative markers MKI67, RRM2, and the survival marker BCL2. LicA reduces pro-tumorigenic aberrations in lipid homeostasis and inflammation through SREBP1. It is a promising non-endocrine candidate for BC prevention. Future studies in immunocompetent BC prevention models are warranted.

Advances in cancer management have improved oncologic outcomes, but the extent of these improvements and disparities across demographic and socioeconomic groups over the past two decades remains unclear. We identified patients diagnosed with primary cancer at eight sites (lung and bronchus, liver and intrahepatic bile ducts [IHBD], esophagus, colon, kidney, pancreas, rectum, and stomach) between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER)-17 database. Kaplan-Meier curves were used to evaluate cancer-specific survival (CSS) across different diagnostic periods, and Cox proportional hazards models were employed to adjust for confounding factors. We found that CSS for eight cancers improved significantly between 2000 and 2019, but the extent of improvement varied by population characteristics. Elderly patients, unmarried individuals, those with low income, and rural residents showed poorer relative CSS improvement across all eight cancers. Relative CSS improvement differences by sex were present across the eight cancers but remained small. Black patients exhibited less relative CSS improvement than White patients only in pancreatic cancer. Absolute 5-year CSS differences by race (White vs. Black) decreased in six cancers except pancreatic and gastric cancers. In summary, the extent of improvement in CSS for the eight cancers varied by demographic characteristics between 2000 and 2019. Absolute survival differences by age, marital status, income, and place of residence widened for most cancers, while racial differences (White vs. Black) narrowed for most cancers. This provides potential recommendations for further adjustments in medical resources.

Selection criteria for lung cancer screening (LCS) are essential for implementing resource- and cost-efficient programs. However, different selection criteria may have similar resource requirements but select dissimilar individuals. This study explores the impact of inclusion criteria on participants' characteristics and health services in Spain. A cross-sectional study was conducted using data from 21,007 individuals from the 2012 Spanish National Health Survey. LCS eligibility was evaluated for four criteria: two from the 4-IN-THE-LUNG-RUN trial (4ITLR1: ages 60-79, 35 pack-years, current smokers or <10 years since cessation; 4ITLR2: ages 60-79, PLCOm2012noRace risk ≥2.6%), the United Kingdom's Targeted Lung Health Check (TLHC: ages 55-74, PLCOm2012noRace risk ≥1.51%), and the United States Preventive Services Task Force (USPSTF: ages 50-80, 20 pack-years, current smokers or <15 years since cessation). Under the most restrictive (4ITLR1) 5.6% of ages 50-80 were eligible, requiring 9.0% additional radiological capacity. Under the broadest (USPSTF) 21.6% of ages 50-80 were eligible, requiring 34.2% additional capacity. All criteria primarily selected men (68.1-82.2% of eligibles). Most criteria favored selecting former smokers (49.4-56.9%). However, eligible women were more often current smokers than men across all criteria (men: 38.5-46.8%, women: 52.7-66.5%). Former smokers smoked more cigarettes per day than current smokers (30 vs. 20) despite having shorter smoking durations, resulting in higher median pack-years across all criteria (range: 44-66). Overall, pack-year-based eligibility decreased with age, while risk-based eligibility was stable across age groups. Different LCS criteria yield populations with highly varied characteristics. Risk-based criteria may provide more equitable eligibility across age groups.

Acute leukemia is the most common type of cancer in children; however, the etiology is poorly understood. The objective of this review was to summarize the current evidence of the role of perinatal factors in the development of acute leukemia. All epidemiological studies published up to October 2023 that evaluated perinatal risk factors for childhood acute leukemia were identified using a multi-tiered approach in two electronic databases (PubMed and Web of Science), without restriction on publication year or language. A total of 85 studies (13 prospective cohort studies, 62 case-control studies, and 10 pooled analyses) were included. We combined the published risk estimates in a meta-analysis, using the Generic Inverse Variance method. An increased risk of acute leukemia and the lymphoblastic subtype (ALL) was associated with high birth weight (>4000 g) (odds ratio [OR] = 1.35; 95% confidence interval [95% CI] 1.20-1.53 and OR = 1.21; 95% CI 1.08-1.34, respectively), maternal history of abortion (OR = 1.27; 95% CI 1.12-1.43 and OR = 1.24; 95% CI 1.08-1.43, respectively), and maternal diabetes (OR = 1.30; 95% CI 1.14-1.48 and OR = 1.32; 95% CI 1.16-1.50, respectively). In addition, an increased risk for ALL was also associated with maternal hypertension (OR = 1.21; 95% CI 1.06-1.38) and cesarean section (OR = 1.10; 95% CI 1.05-1.16). Our review suggests a potential role for perinatal factors in the development of acute leukemia in children. These findings indicate potential avenues for developing cost-effective prevention strategies applicable at the population level, while the mechanism of action is investigated.