Int. J. Cancer [JOURNAL]
Sun
200 papers
SGLT2 inhibitors mitigate cardiorenal toxicity and improve survival in type 2 diabetes mellitus patients undergoing antineoplastic therapy: A multicenter retrospective cohort study.
Zhao Y, Zhang Y, Ju M … +1 more , Liu Y
Int J Cancer · 2026 Jul · PMID 41856758 · Publisher ↗
Asia faces a rising cancer burden, with type 2 diabetes mellitus (T2DM) prevalence in cancer patients at 24.4% (2.3-fold higher than that of the general population). Antineoplastic therapies (e.g., anthracyclines and vas...
Asia faces a rising cancer burden, with type 2 diabetes mellitus (T2DM) prevalence in cancer patients at 24.4% (2.3-fold higher than that of the general population). Antineoplastic therapies (e.g., anthracyclines and vascular endothelial growth factor receptor [VEGFR] inhibitors) increase cardiorenal toxicity, exacerbated by T2DM. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefit non-oncologic populations but are understudied in T2DM-cancer patients. We assessed SGLT2i's effects on antineoplastic-related cardiorenal toxicity/survival via a multicenter retrospective cohort of 248 T2DM-cancer patients (56.0% male, mean age 66.7 years) 1:1 divided into SGLT2i/non-SGLT2i groups. Over 30.4 months of follow-up, SGLT2i reduced cardiovascular events by 86.1% (odds ratio [OR] = 0.139, 95% CI 0.027-0.710, p = .018) and all-cause mortality by 84.7% (HR = 0.153, 95% CI 0.055-0.431, p < .001). Echocardiography showed improved left ventricular ejection fraction (LVEF) and reduced left ventricular end-diastolic diameter (LVID)/left atrial (LA) dimensions (all p < .001). Despite lower baseline estimated glomerular filtration rate (eGFR) in the SGLT2i group, SGLT2i preserved renal function (post-treatment eGFR: 99.8 vs. 67.5 mL/min/1.73 m; p = .054) and reduced uric acid (UA) levels by 23.6% (p < .001). Benefits persisted across solid tumor/hematological malignancies and anthracycline-based therapy, targeted antineoplastic therapy or immunotherapy subgroups, with no increase in infection. SGLT2i improve cardiorenal outcomes and survival in T2DM-cancer patients warranting prospective validation.
Prediction of dose reductions and impact of reduced starting doses of CDK4/6i on effectiveness in HR-positive/HER2-negative metastatic breast cancer: Real-world data from the OPAL registry.
Marschner P, Ringwald K, Thill M … +17 more , Zahn MO, Welt A, Nusch A, Kaltenecker G, Rodemer Y, Hagen V, Schock C, Kruggel L, Kaiser-Osterhues A, Klein D, Haug N, Stickeler E, Harbeck N, Wöckel A, Marschner N, Decker T, OPAL Registry Group
Int J Cancer · 2026 Jul · PMID 41851017 · Full text
Cancer patients prone to toxicities might benefit from dose reduction over fixed-dose recommendations. We develop a predictive index to identify patients with increased probability of dose reduction, intolerable toxiciti...
Cancer patients prone to toxicities might benefit from dose reduction over fixed-dose recommendations. We develop a predictive index to identify patients with increased probability of dose reduction, intolerable toxicities, or therapy discontinuation (hereafter: dose reduction) in metastatic breast cancer (MBC) and compare real-world effectiveness of reduced (RSD) versus full starting dose (FSD) using this index. This analysis included 618 patients with HR-positive, HER2-negative MBC from the prospective, observational, multicenter registry OPAL (NCT03417115), receiving first-line palbociclib (n = 386) or ribociclib (n = 232) plus endocrine therapy. A logistic regression model was employed to derive the predictive index. Inverse probability of treatment weighting was used to emulate a head-to-head comparison of RSD and FSD by analyzing progression-free (PFS) and overall survival (OS). Within 6 months, 215 patients (35%) underwent dose reduction, including 109 (51%) with RSD. Predictors for dose reduction were age ≥65 years and Charlson comorbidity index (CCI) ≥1. Among patients with increased probability of dose reduction (index ≥1: ≥65 years and/or CCI ≥ 1), median PFS and OS were 30.1 [21.7, 54.0] and 57.6 [40.0, NA] months with RSD vs. 29.3 [24.9, 32.0] and 43.1 [38.8, 50.3] months with FSD. For low-probability patients (index = 0: <65 years and CCI = 0), median PFS and OS were 17.6 [9.1, 29.8] and 32.9 [23.1, 40.9] months with RSD vs. 24.5 [19.8, 32.0] and 54.2 [48.8, NA] months with FSD. In this real-world MBC setting, patients ≥65 years and/or with CCI ≥ 1 had an increased probability of dose reduction and may benefit from RSD, as this yielded outcomes comparable to FSD. Younger, fitter patients may require full dosing. Future studies, ideally randomized controlled trials, should aim to confirm these findings.
Methodological reflections on real-world electronic health records analyses in oncology.
Bjerrum A
Int J Cancer · 2026 Jul · PMID 41851015 · Publisher ↗
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Dynamics of the association between circulating levels of miRNA and pancreatic cancer risk through the years prior to pancreatic cancer diagnosis.
Cai H, Setiawan VW, Guo X … +8 more , Wu J, Stolzenberg-Solomon R, Gao YT, Berlin J, Ye F, Cai Q, Zheng W, Shu XO
Int J Cancer · 2026 Jul · PMID 41845595 · Full text
Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is critical to improving the overall prognosis. However, biomarkers for early diagnosis are lacking. We used pre-diagnostic plasma samples from 1307 PDAC cases a...
Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is critical to improving the overall prognosis. However, biomarkers for early diagnosis are lacking. We used pre-diagnostic plasma samples from 1307 PDAC cases and individually matched cancer-free controls from five prospective cohort studies. Conditional logistic regression was used to assess the association of circulating miRNAs with PDAC risk. Linear regression was conducted to identify miRNAs ratio (miRNA levels of case over their matched control) change associated with the lead time from blood draw to PDAC diagnosis. We found 20 miRNAs significantly associated with PDAC risk (p < .05). Among them, 13 miRNAs showed a significant ratio change within 10 years prior to cancer diagnosis. The case-control difference of miR-155-5p and miR-493-3p increased when blood draw was closer to PDAC diagnosis. While the ratio changes of the remaining 11 miRNAs decreased. Adding 13 miRNAs to known risk factors and CA19-9 significantly improved the prediction performance for imminent PDAC risk, with AUCs of 85%, 77%, and 73% during the time windows of 1, 2, and 3 years prior to PDAC diagnosis. Findings of this large prospective study shield a light on the biology of PDAC and suggest a potential utility of monitoring circulating miRNAs for PDAC risk surveillance among high-risk individuals.
Drug repurposing in oncology: Bridging computational discovery to clinical application.
Baskar S, Prasad NR
Int J Cancer · 2026 Jul · PMID 41839763 · Publisher ↗
Drug repurposing, the identification of new therapeutic applications for existing drugs, has emerged as a pragmatic and cost-efficient strategy to accelerate oncology drug discovery. Faced with rising development costs,...
Drug repurposing, the identification of new therapeutic applications for existing drugs, has emerged as a pragmatic and cost-efficient strategy to accelerate oncology drug discovery. Faced with rising development costs, protracted timelines, and high attrition rates associated with traditional de novo drug development, repurposing leverages known pharmacokinetics, safety profiles, and manufacturing processes to expedite clinical translation. This review synthesizes current advances in computational and experimental methodologies and mechanistic insights that drive drug repurposing for cancer therapy. In silico strategies, including molecular docking, machine learning, transcriptomic-proteomic signature reversal, and network-based modeling, have enabled rapid identification of repurposable agents by mining multi-omics and historical pharmacological data. Experimental pipelines spanning high-throughput screening, phenotypic assays, biochemical validations, and functional animal models remain essential to establish efficacy and delineate mechanisms of action. Notably, repurposed drugs exhibit anticancer activity by modulating key pathways, including phosphatidylinositol 3-kinase/Ak strain transforming/mechanistic target of rapamycin, mitogen-activated protein kinase/extracellular signal-regulated kinase, wingless-related integration site/β-catenin signaling, as well as redox homeostasis and DNA response. Despite their promise, repurposed candidates face barriers including limited intellectual property protections, dose optimization challenges, and regulatory uncertainty. Moreover, clinical translation is often hindered by insufficient mechanistic understanding and a lack of predictive biomarkers. Integration of multi-omics datasets, explainable artificial intelligence, patient-derived organoids, and clustered regularly interspaced short palindromic repeats-based genetic screens now offers unprecedented precision in identifying context-specific drug effects and synthetic lethal interactions. With cancer causing one in six global deaths and marked by therapeutic resistance and molecular heterogeneity, drug repurposing provides a scalable solution. This approach bridged preclinical insight with clinical application, potentially transforming cancer therapeutics through rational, data-driven innovation.
Sequential personalized neoantigen vaccination following first-line treatments demonstrates safety and efficacy in advanced hepatocellular carcinoma.
Cai Z, Qiu L, Li L … +14 more , Li Z, Zhang K, Lin Y, Zhou Y, Dong X, Chen G, Xie R, Lin J, Zeng Y, Yu H, Fang Z, Guo W, Huang X, Liu X
Int J Cancer · 2026 Aug · PMID 41839756 · Publisher ↗
Hepatocellular carcinoma (HCC) has limited therapeutic options in the advanced stages; although first-line combinations of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and/or programmed c...
Hepatocellular carcinoma (HCC) has limited therapeutic options in the advanced stages; although first-line combinations of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and/or programmed cell death protein 1 (PD-1) inhibitors show promise, their efficacy is constrained by inadequate tumor-specific T-cell infiltration. To address this limitation, we conducted an investigator-initiated, single-center clinical trial (ChiCTR2300067818) evaluating the safety, feasibility, and preliminary efficacy of sequential personalized neoantigen vaccination following TACE plus TKI/PD-1-based therapy in patients with advanced HCC. Whole-exome and transcriptome sequencing identified patient-specific neoantigens, which were synthesized as long peptides and formulated with dual adjuvants for subcutaneous administration. Among 10 initially enrolled patients, 4 received personalized vaccination after comprehensive screening, with 2 patients (N03 and N04) completing the full 8-injection vaccination regimen. Sequential neoantigen vaccination demonstrated excellent safety profiles, with only mild injection-site reactions observed. Both patients achieved partial response following vaccination. Interferon-gamma Enzyme-Linked ImmunoSpot assays confirmed robust neoantigen-specific responses against multiple peptide pools in both patients. Dynamic monitoring revealed that serum alpha-fetoprotein and Des-gamma-carboxy prothrombin levels correlated with clinical responses, declining significantly during vaccination. These findings demonstrate that sequential personalized neoantigen vaccination following first-line TACE-based therapy is safe, feasible, and capable of inducing potent tumor-specific immune responses, supporting further investigation in larger clinical trials.
Cyanotoxin exposure as a novel risk factor for liver fibrosis and steatosis.
Hernandez BY, Zhu X, Macatugal E … +7 more , Nagata M, Garvin K, Paulino YC, Wilkens LR, Wong LL, David AM, Biggs L
Int J Cancer · 2026 Aug · PMID 41833562 · Publisher ↗
Cyanobacteria are ubiquitous environmental bacteria capable of producing cyanotoxins, including potent liver tumor promoters. There is limited knowledge of exposure to cyanotoxins and their potential role in the pathogen...
Cyanobacteria are ubiquitous environmental bacteria capable of producing cyanotoxins, including potent liver tumor promoters. There is limited knowledge of exposure to cyanotoxins and their potential role in the pathogenesis of liver cancer The relationship of cyanotoxin exposure with two hallmarks of progressive liver disease-liver fibrosis and steatosis-was evaluated in a cross-sectional study of 399 adult residents of the state of Hawaii and the US territory of Guam without a history of cancer. Microcystins (MC), nodularins (NOD), cylindrospermopsin (CYN), and anabaenopeptins (AB) were analyzed in saliva, serum, and urine using direct competitive enzyme-linked immunosorbent assays. Liver fibrosis and steatosis were measured by transient elastography. Linear and non-linear associations of cyanotoxin levels with degree of fibrosis and steatosis were evaluated in multivariate generalized linear and additive models. One or more cyanotoxins were variably detected in all individuals. Moderate to severe fibrosis or cirrhosis was present in 18% and moderate to severe steatosis in 53%. Positive associations with fibrosis level were observed for salivary cyanotoxins: MC/NOD (linear: β = 9.07, 95% confidence interval [CI] 1.32-16.82, p = .022; non-linear p = .0011); CYN (linear: β = 24.21, 95% CI 14.12-34.30, p < .0001; non-linear p = .0001); AB (non-linear p = .0125). A positive association with steatosis level was observed for serum MC/NOD (non-linear p = .0120). Non-linear associations of cyanotoxins with fibrosis were specific to defined concentrations. Our novel findings suggesting that cyanotoxins are independent risk factors for liver disease are consistent with our prior study linking oral cyanobacteria to hepatocellular carcinoma and may have global implications for liver cancer prevention.
Impact of non-genetic heterogeneity of BRAF-mutant colon cancer organoids on growth kinetics, drug sensitivity and Wnt dynamics.
Zieger V, Woehr E, Traichel J … +4 more , Brummer T, Zengerle R, Kartmann S, Zimmermann S
Int J Cancer · 2026 Jul · PMID 41833556 · Full text
Patient-derived organoid (PDO) models are powerful systems for studying tumor biology and drug response. By retaining genetic, histological, and functional characteristics of the original tumor, including intra- and inte...
Patient-derived organoid (PDO) models are powerful systems for studying tumor biology and drug response. By retaining genetic, histological, and functional characteristics of the original tumor, including intra- and interpatient heterogeneity, they provide powerful tools to investigate therapy resistance. While genomic profiling is well established in organoid-based screening, non-genetic parameters such as organoid size, seeding density, and morphology remain underexplored, despite their potential to influence functional readouts. Here, we systematically examined how these factors affect proliferation, drug sensitivity, and Wnt responses in a murine colorectal cancer organoid model carrying oncogenic Apc, Braf, and Trp53 mutations. Using our automated Pick-Flow-Drop handling platform, we implemented a reproducible plating workflow enabling precise control over organoid selection and screening conditions. We found that higher seeding density and larger organoid size reduced metabolic activity and decreased sensitivity to the MEK inhibitor trametinib. Moreover, distinct morphological subgroups, such as solid and cystic organoids, displayed differential drug responses under growth factor-deprived conditions, correlating with distinct Wnt-3a profiles in the culture supernatant. Solid organoids were more trametinib-sensitive and exhibited higher Wnt-3a levels, suggesting divergent cell compositions and pathway dependencies. Our findings highlight the functional relevance of non-genetic variability in organoid cultures and establish a framework to improve reproducibility and biological insight in PDO-based drug screening.
Real-world effectiveness and safety with nivolumab plus ipilimumab or nivolumab alone in patients with or without melanoma brain metastasis: Results from the German noninterventional NICO study.
Gutzmer R, Weichenthal M, Eigentler T … +16 more , Mohr P, Sickmann T, Dücker P, Gebhardt C, Haferkamp S, Kähler KC, Meier F, Pföhler C, Sindrilaru A, Terheyden P, von Wasielewski I, Ugurel S, Ulrich J, Utikal J, Weishaupt C, Schadendorf D
Int J Cancer · 2026 Aug · PMID 41833546 · Publisher ↗
The prospective, German NICO study (ClinicalTrials.gov identifier: NCT02990611) evaluated real-world effectiveness and safety with nivolumab plus ipilimumab or nivolumab alone (any-line) in patients with advanced melanom...
The prospective, German NICO study (ClinicalTrials.gov identifier: NCT02990611) evaluated real-world effectiveness and safety with nivolumab plus ipilimumab or nivolumab alone (any-line) in patients with advanced melanoma with/without melanoma brain metastasis (MBM). A total of 755 patients treated with nivolumab plus ipilimumab (n = 486; median follow-up, 46.8 months) or nivolumab alone (n = 269; median follow-up, 38.7 months) were enrolled. Baseline characteristics differed between the treatment groups, with the nivolumab plus ipilimumab group being younger and having poorer prognostic factors. At baseline, 221 patients (29.3%) had MBM, among whom 15 patients had symptomatic MBM based on dexamethasone use. In patients with/without MBM receiving first-line nivolumab plus ipilimumab, objective response rates (ORRs) were 46.2% and 54.0%, respectively; 3-year overall survival (OS) rates were 34.0% and 47.0%. In patients with/without MBM receiving first-line nivolumab alone, ORRs were 61.5% and 55.1%, respectively; 3-year OS rates were 42.7% and 47.8%. In a 3-month landmark analysis, patients with MBM with a complete/partial response demonstrated 3-year OS rates of 71.9% with nivolumab plus ipilimumab and 89.6% with nivolumab alone. Three-year OS rates were 42.2% and 20.0% with asymptomatic and symptomatic MBM, respectively. There were no substantial differences in the rates of serious grade 3/4 treatment-related adverse events between patients with/without MBM. HRQoL was stable. Results from this real-world study show that a substantial proportion of patients with MBM derive long-term benefit from nivolumab plus ipilimumab or nivolumab alone, particularly those with asymptomatic MBM.
Lung cancer as a global health challenge: Multidimensional biomarker research and therapeutic advances.
Jin D, Zhong L, Chen L
Int J Cancer · 2026 Jul · PMID 41826059 · Publisher ↗
Lung cancer, the leading cause of global cancer-related mortality, is categorized into small-cell and non-small-cell subtypes. The heterogeneous non-small-cell lung cancer group is further subcategorized primarily into a...
Lung cancer, the leading cause of global cancer-related mortality, is categorized into small-cell and non-small-cell subtypes. The heterogeneous non-small-cell lung cancer group is further subcategorized primarily into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, each underpinned by distinct molecular alterations. Although traditional serum biomarkers aid in subtype differentiation and treatment monitoring, their utility is limited by challenges such as poor specificity due to inflammatory confounders and the difficulty of dynamically tracking therapeutic resistance. Recent advances have identified emergent subtype-specific biomarkers that reflect metabolic reprogramming, epigenetic dysregulation, stemness signatures, and interactions within the immune microenvironment. By integrating analytes such as ctDNA, exosomal RNAs, and urinary DNA with multi-analyte panels and advanced imaging, liquid biopsies offer a promising avenue to enhance early detection accuracy, prognostication, and dynamic therapy monitoring. Nevertheless, the clinical adoption is hindered by several challenges, including incomplete validation, the need for technical standardization, intratumoral heterogeneity, and inter-ethnic variability. The convergence of artificial intelligence (AI)-enhanced multi-omics with biomarker-guided therapeutics represents a transformative strategy with the potential to overcome resistance, mitigate ethnic disparities, and ultimately transform lung cancer into a chronic, manageable disease. Therefore, prioritizing clinically validated AI-integrated platforms is pivotal to achieve precision oncology.
Treatment patterns and clinical outcomes in real-world patients with small-cell lung cancer in South Korea: A single-center experience.
Park S, Kang D, Lee J … +9 more , Jung HA, Sun JM, Lee SH, Ahn JS, Lee H, Lim H, Pundole X, Cho J, Ahn MJ
Int J Cancer · 2026 Aug · PMID 41826057 · Publisher ↗
We examined treatment patterns and overall survival (OS) among patients with small-cell lung cancer (SCLC) in South Korea. This retrospective cohort study included patients with SCLC treated at Samsung Medical Center bet...
We examined treatment patterns and overall survival (OS) among patients with small-cell lung cancer (SCLC) in South Korea. This retrospective cohort study included patients with SCLC treated at Samsung Medical Center between January 1, 2018 and December 31, 2021, with follow-up through March 13, 2023. The first systemic therapy after initial diagnosis was defined as first-line, with subsequent lines identified by initiation of new regimens. Survival outcomes were estimated from the start of each treatment line. Among 515 patients, 343 had extensive-stage (ES) and 172 had limited-stage (LS) at diagnosis. Platinum-based regimen without anti-PD-L1 was the most common first-line regimen for both groups; however, use of anti-PD-L1 containing platinum regimens increased markedly from 2020 onward in patients with ES-SCLC. In the second line setting, 64% of patients with ES-SCLC received platinum-based therapy and 31% irinotecan monotherapy, whereas taxanes were predominantly used in patients with LS-SCLC (51.7%). Median OS for ES-SCLC following first-line treatment was 11.3 months (95% CI: 9.7, 12.2) [11.4 months (95% CI: 9.6, 12.8) with anti-PD-L1 vs. 11.1 months (95% CI: 9.2, 12.5) without], and 29.8 months (95% CI: 23.6, 46.6) months following first definitive therapy for LS-SCLC. Median OS declined to 6.9 months (95% CI: 6.3, 7.9) after second line therapy in ES-SCLC and 12.1 months (95% CI: 7.9, 17.1) in patients with LS-SCLC following 1L therapy after initial definitive therapy. These findings characterize the evolving SCLC treatment landscape, underscore the limited effectiveness of current treatment options, and highlight the persistent poor prognosis in this population.
Cancer care in Afghanistan: A comprehensive analysis of opportunities and challenges in a low-income and conflict-affected country.
Abdullah M, Hashimi I, Bump JB … +6 more , Rebbeck TR, Fadhil I, Paktin M, Jobanputra K, Arwal SH, Camacho R
Int J Cancer · 2026 Aug · PMID 41823122 · Publisher ↗
The main purpose of this study was to assess the cancer prevention and control capacity in Afghanistan. The study utilized the WHO/IAEA National Cancer Control Programmes (NCCP) Core Capacity Self-Assessment Tool to eval...
The main purpose of this study was to assess the cancer prevention and control capacity in Afghanistan. The study utilized the WHO/IAEA National Cancer Control Programmes (NCCP) Core Capacity Self-Assessment Tool to evaluate Afghanistan's cancer control capacity, shortages, and priorities. Data collection involved site visits to 12 public and five private healthcare facilities conducted by a multidisciplinary team of nine experts between June and July 2021. This was complemented by a structured questionnaire survey, desk review, and literature review, which continued until January 2025. The findings reveal significant gaps in cancer control capacity in Afghanistan. The country lacks a national cancer control plan, and there are no established programs for cancer screening and early detection. Diagnostic and treatment services are predominantly concentrated in urban centers, with limited access to essential medicines, radiology, pathology, and systemic therapies. Palliative care services are nearly non-existent, and radiotherapy facilities are absent. While Afghanistan has made initial strides in cancer control, significant challenges remain in developing a comprehensive and sustainable cancer control program. Immediate priorities include finalizing and implementing a national cancer control plan, expanding diagnostic and treatment infrastructure, integrating palliative care, and strengthening workforce capacity. This assessment is crucial not only for Afghanistan but also offers valuable insights for other resource-constrained countries facing similar challenges. Regionally, it highlights the importance of coordinated efforts in South Asia and the Middle East to tackle cancer collaboratively. Globally, these findings underscore the need for international investment and technical assistance to address cancer as a shared public health priority.
Efficacy and safety of neoadjuvant apatinib plus PD-1 inhibitor with SOX for locally advanced gastric cancer: A multicenter, retrospective cohort study.
Ding S, Huang H, Cao C … +4 more , Liu C, Zhong W, Xie Y, Yu J
Int J Cancer · 2026 Aug · PMID 41823111 · Publisher ↗
Although neoadjuvant PD-1 inhibitors combined with chemotherapy are promising for locally advanced gastric cancer (LAGC), pathological complete response (pCR) rates remain suboptimal. This multicenter retrospective study...
Although neoadjuvant PD-1 inhibitors combined with chemotherapy are promising for locally advanced gastric cancer (LAGC), pathological complete response (pCR) rates remain suboptimal. This multicenter retrospective study (January 2020-September 2024) evaluated the synergistic potential of adding apatinib to the neoadjuvant framework of PD-1 inhibitors plus SOX chemotherapy (PA-SOX) versus the doublet regimen (P-SOX). From a multi-institutional cohort of 449 patients, 1:1 propensity score matching (PSM) was employed to yield 102 well-balanced pairs. The PA-SOX regimen demonstrated a significantly superior primary endpoint, achieving a pCR rate of 17.6% compared to 6.9% in the P-SOX group (p = 0.031; FDR-adjusted p = 0.036). This pathological advantage was further reflected in significantly higher major pathological response (MPR; 38.2% vs. 15.7%, p < 0.001) and objective response rates (ORR; 62.7% vs. 33.3%, p < 0.001). Survival analysis demonstrated improved 2-year overall survival (82.4% vs. 69.9%; HR = 0.32, 95% CI: 0.15-0.66; p = 0.001) and disease-free survival (71.1% vs. 41.7%; HR = 0.35, 95% CI: 0.22-0.57; p < 0.001). Safety profiles were manageable, with no significant increase in Grade 3-4 adverse events (p = 0.503) or postoperative morbidity (p = 0.718), supported by a standardized preoperative washout protocol. Multivariate analysis confirmed PA-SOX as an independent protective factor for survival. In conclusion, these retrospective findings suggest that adding apatinib to the neoadjuvant immunochemotherapy backbone may optimize pathological responses and enhance short-term survival for LAGC with a tolerable safety profile; however, the durability of these survival benefits warrants validation in large-scale, randomized phase III trials.
Quantifying the contribution of modifiable risk factors for progression of MGUS to multiple myeloma in a Veteran population.
Wang M, Sigel B, Liu L … +9 more , Huber JH, Ji M, Schoen MW, Sanfilippo KM, Thomas TS, Colditz GA, Hsu SH, Wang SY, Chang SH
Int J Cancer · 2026 Aug · PMID 41813601 · Full text
Multiple myeloma (MM) is the most common plasma cell dyscrasia in the United States with tremendously high burden. MM is preceded by a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). Al...
Multiple myeloma (MM) is the most common plasma cell dyscrasia in the United States with tremendously high burden. MM is preceded by a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). Although several risk factors for progression have been identified (e.g., older age, male sex, black race, obesity, chemical exposure), their relative contributions remain unclear. Unlike other malignancies, such evidence is lacking for MM despite its high burden. To identify potential intervention strategies that can effectively prevent progression in patients with MGUS, we quantified contributions of the identified modifiable risk factors in the United States Veteran population with MGUS. Compared to the general population, this population is particularly vulnerable to MM as its higher proportions of male and older age as well as the potential prior Agent Orange exposure. We conducted a retrospective cohort study in the Veterans Health Administration and calculated multivariable-adjusted population attributable fractions (aPAFs) of progression accounting for competing risk of death. The aPAF estimates the proportion of progression burden in the population with MGUS that is statistically attributable to a specific risk factor, independent of other factors. In the cohort of 35,073 Veterans with MGUS, among all evaluated risk factors (both modifiable and non-modifiable), excess body mass index (BMI ≥25 kg/m) was the leading factor (Black: aPAF = 27.1%, 95% CI 19.5%-34.0%; White: 27.2%, 95% CI 20.3%-33.4%; All: aPAF = 27.1%, 95% CI 22.1%-31.9%). Our study highlights the potential of weight management and lifestyle modification for informing the design of targeted MM prevention strategies for Veterans diagnosed with MGUS.
ULK4 and CDKN2A polymorphisms influence the risk of developing monoclonal gammopathy of undetermined significance.
Sánchez-Maldonado JM, Macauda A, Cabrera-Serrano AJ … +52 more , Thomsen H, Güler M, Horst RT, van Guelpen B, Vodicka P, Landi S, Chattopadhyay S, Ünal P, Ruiz-Durán L, Casabonne D, Goldschmidt H, Serin I, Carretero-Fernández M, Cabezudo E, Reyes-Zurita F, Norman AD, García-Sanz R, Capurso G, Hoffmann P, Pettersson-Kymmer U, Jiménez-Romera F, Rajkumar SV, Weinhold N, Vodickova L, Langer C, Stein A, Karismaz A, Moreno V, Nöthen MM, Jöckel KH, Tavano F, Martínez-López J, Kumar SK, Gutiérrez-Bautista JF, Basso D, Späth F, Benavente Y, Hildebrandt MAT, Schmidt B, Sevcikova T, Reis RMV, Li Y, López-Nevot MÁ, Netea MG, Campa D, Clay-Gilmour A, Slager SL, Hemminki K, Vachon CM, Försti A, Canzian F, Sainz J
Int J Cancer · 2026 Jul · PMID 41813586 · Full text
Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor condition to multiple myeloma (MM). Given the role of autophagy in modulating MM risk, we investigated whether genetic variation in autop...
Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor condition to multiple myeloma (MM). Given the role of autophagy in modulating MM risk, we investigated whether genetic variation in autophagy-related genes influences susceptibility to MGUS. We analyzed the association of 34,042 common autophagy-related single nucleotide polymorphisms (SNPs) with MGUS across six independent cohorts, five from Europe and one from North America, comprising 2317 MGUS cases and 282,358 controls. We also assessed their impact on immune parameters, including absolute counts of 91 blood-derived immune cell subsets and 103 circulating immunological proteins. Meta-analysis revealed a genome-wide significant association between the ULK4 allele and increased MGUS risk (p = 3.35 × 10). Carriers of this allele showed reduced counts of memory B cell subsets (IgM+CD38+CD27+ and IgD+IgM+CD27+; p = .0038 and p = .0056, respectively) and natural effector B cells (CD24+CD38+IgD+IgM+ cells; p = .0060). Although these associations were not statistically significant after multiple testing correction, they suggest a role of ULK4 in early B-cell differentiation. Additionally, the CDKN2A variant showed a suggestive association with MGUS risk (p = 2.17 × 10), affecting transcription factor binding involved in B-cell proliferation and differentiation, although it lacked association with immune markers. In conclusion, we confirm a genome-wide significant association of the ULK4 locus and MGUS risk, supporting its role in early B-cell differentiation, and identify CDKN2A as a candidate susceptibility locus warranting further investigation.
Interplay between ER stress and DNA repair pathways in solid tumors under hypoxia.
Jadhav A, Singh N
Int J Cancer · 2026 Aug · PMID 41804218 · Publisher ↗
Solid tumors often develop a hypoxic microenvironment that triggers adaptive cellular responses, promoting tumor progression, aggressiveness, and therapeutic resistance. Hypoxia activates HIF1α, a key regulator that modu...
Solid tumors often develop a hypoxic microenvironment that triggers adaptive cellular responses, promoting tumor progression, aggressiveness, and therapeutic resistance. Hypoxia activates HIF1α, a key regulator that modulates the expression of genes involved in metabolic reprogramming and angiogenesis. Hypoxia disrupts protein homeostasis by compromising endoplasmic reticulum (ER) function, resulting in ER stress (ERS) and subsequent activation of the ER stress response (ERSR), collectively known as the unfolded protein response (UPR). Hypoxic stress also induces DNA damage and genomic instability, driven by replication stress and dysregulated DNA damage repair (DDR) pathways. In this review, we examine the current understanding of the mechanisms by which UPR sensors interface with DDR components to influence cancer cell fate under hypoxic conditions. Elucidating the mechanistic crosstalk among these hypoxia-responsive stress pathways will provide a better understanding of tumor evolution and metastasis. Furthermore, it highlights the cellular vulnerabilities emerging from this interplay that may be leveraged for therapeutic interventions.
Trends in the incidence of cancers of the breast and female genital tract in Harare, Zimbabwe 1990-2019.
Chokunonga E, Chirenje ZM, Borok M … +5 more , Makunike-Mutasa R, Ndlovu N, Mudavanhu J, Liu B, Parkin DM
Int J Cancer · 2026 Aug · PMID 41803021 · Full text
Trends in age standardised incidence rates (ASRs) in the black (African) female population of Harare are reported for five cancers-of the breast and genital tract (cervix and corpus uteri, ovary and vulva) over a 30-year...
Trends in age standardised incidence rates (ASRs) in the black (African) female population of Harare are reported for five cancers-of the breast and genital tract (cervix and corpus uteri, ovary and vulva) over a 30-year period. The incidence of cervix cancer is very high (ASR of 73.7 per 10) and has increased at a rate of 1% annually over the period, although remaining stable in the most recent 15 years; the increase involves mainly women born between 1950 and 1970. Breast cancer rates are less than half those of cervix, but the increase has been more dramatic-3% annually-although this seems to involve only women aged over 40. The incidence of ovarian cancer has been constant over the 30 years; there was a small increase in the incidence of cancer of the corpus uteri (1.5% annually) and a more marked one for vulvar cancer (5.6% annually), for which the incidence is relatively high, by global standards. Concurrent with the increasing incidence of cancers of the breast and corpus uteri are notable trends of population risk factors such as rising obesity rates and declining fertility. The elevated burden of cervix and vulvar cancers aligns with patterns observed in populations with high HPV prevalence, though population-specific data remain limited. The results confirm that cancers associated with increasingly affluent lifestyles (breast and corpus uteri) are increasing, although the incidence of cancer of the cervix-an eminently preventable cancer-remains persistently high and is clearly a priority for cancer control.
Nationwide audit of cervical cancer screening reveals unsatisfactory triage strategies and trends over time in incidence among cytology negative women.
Kärrberg C, Gray P, Elfgren K … +7 more , Milerad H, Andrae B, Lei J, Sparén P, Dillner J, Wang J, Elfström KM
Int J Cancer · 2026 Jul · PMID 41803020 · Full text
Regular audits are essential for monitoring and evaluation of cervical screening. We audited the Swedish cervical screening program during the transition to HPV-based screening using a registry-based cohort design. In to...
Regular audits are essential for monitoring and evaluation of cervical screening. We audited the Swedish cervical screening program during the transition to HPV-based screening using a registry-based cohort design. In total, 5689 consecutive, confirmed cases of invasive cervical cancer between 2012 and 2022 were retrieved from the Swedish Quality Register for Gynecological Cancer. Their screening history, screening status, invitations to cervical screening, all diagnoses in screening cytology and HPV genotypes were retrieved from the Swedish National Cervical Screening Registry. Furthermore, all cancer cases during 2018-2022 were classified according to their screening history and the age-standardized cervical cancer incidence rate stratified by screening history and calendar year was calculated among the cohort of all women in Sweden ages 29-84. Non-participation remains the main process related history with high risk of cancer (cervical cancer incidence rate, IR, among non-attenders was 33.9 [95% confidence intervals, 95% CI, 28.2-39.5] per 100,000 person-years, /100,000PY, representing 31% of cases in 2022). The cervical cancer IR after negative cytology increased with calendar time (IR = 5.5 [95% CI, 4.1-6.8]/100,000PY in 2012 and 11.5 [8.1-14.9]/100,000PY in 2022) and was high after a positive HPV test followed by negative cytology triage (IR = 56.7 [39.9-73.6] in 2022). In conclusion, this comprehensive audit has identified a decreasing protection by the screening test under discontinuation (cytology) and that the performance as a triage test after HPV-testing is unsatisfactory.
A cost-effectiveness analysis of breast cancer treatment in certified versus non-certified hospitals in Germany.
Lwin MW, Schoffer O, Streissnig C … +18 more , Wimberger P, Gerken M, Bierbaum V, Bobeth C, Rößler M, Dröge P, Ruhnke T, Günster C, Tol KK, Link T, Scharl A, Sturm-Inwald EC, Kast K, Papathemelis T, Ortmann O, Klinkhammer-Schalke M, Schmitt J, Schlander M
Int J Cancer · 2026 Jul · PMID 41802986 · Full text
In Germany, the German Cancer Society (Deutsche Krebsgesellschaft [DKG]) accredits hospitals to ensure high-quality cancer treatment through adherence to clinical guidelines and a multidisciplinary approach. Evidence sug...
In Germany, the German Cancer Society (Deutsche Krebsgesellschaft [DKG]) accredits hospitals to ensure high-quality cancer treatment through adherence to clinical guidelines and a multidisciplinary approach. Evidence suggests certified hospitals (CHs) achieve better clinical outcomes and prognoses than non-certified hospitals (NCHs). However, additional services required for certification incur substantial, unreimbursed costs, necessitating a focused cost-effectiveness evaluation. This retrospective cohort study utilized anonymized administrative routine healthcare data from Allgemeine Ortskrankenkasse, Germany's largest statutory health insurance. The study sample comprised 143,720 incident breast cancer (BC) patients treated between 2009 and 2017 across both CHs and NCHs. A health system perspective was used in this cost-effectiveness analysis. Direct medical costs (inpatient, outpatient, medication, and certification) were compared between CHs and NCHs. Life-years gained (LYG) were calculated from 5-year restricted mean survival time. The incremental cost-effectiveness ratio (ICER), quantified as cost per LYG, served as the primary outcome measure, reported in 2024 euro. Treatment in CHs significantly improved breast cancer survival, yielding 201 LYG per 1000 patients (95% confidence interval: 185-216). Accounting for €1.5 M in certification-related costs and marginal direct medical costs, the total incremental cost was €1.81 M per 1000 patients. This resulted in an ICER of €9036 per LYG. Despite the financial investment required for DKG certification, BC treatment in CHs provided significant survival benefits at a reasonable incremental cost, reinforcing the clinical and economic value. These findings offer critical insights for hospital authorities and healthcare policymakers, supporting the continued investment in certification.
Cyclin-dependent kinases as therapeutic targets in cancer: Recent advances, challenges, and opportunities.
Ju N, Zhao L, Yin S … +4 more , Yang X, Zhou J, Gao J, Qi F
Int J Cancer · 2026 Aug · PMID 41795212 · Publisher ↗
Dysregulated cell cycle progression drives uncontrolled proliferation and is a fundamental hallmark of cancer, making cyclin-dependent kinases (CDKs), which largely govern cell-cycle progression and cell division, attrac...
Dysregulated cell cycle progression drives uncontrolled proliferation and is a fundamental hallmark of cancer, making cyclin-dependent kinases (CDKs), which largely govern cell-cycle progression and cell division, attractive therapeutic targets. Currently, CDK inhibitors (CDKIs), particularly agents targeting CDK4/6, have shown clinical activity in HR/HERmetastatic breast cancer. Recent structural elucidation of the CDK2 catalytic domain and its allosteric sites has enabled the development of several selective CDK2 inhibitors, many of which have exhibited encouraging antitumor activity. Moreover, emerging evidence further indicates that dual inhibition of CDK4/6 and CDK2 can synergistically overcome resistance to CDK4/6 blockade. Notably, recent studies have revealed that CDKIs can induce cellular senescence and enhance the efficacy of cancer immunotherapy. In this review, we outline the CDK family and their key functions in cell cycle control, summarize recent clinical advances in CDKI-based therapies, with emphasis on CDK4/6 and CDK2 inhibition, and discuss opportunities to integrate CDK-targeted therapy with immunotherapy and other therapeutic strategies.
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