Cancer imposes substantial clinical and financial burdens worldwide. Although Korea operates a universal National Health Insurance system, concerns remain regarding healthcare utilization and out-of-pocket (OOP) costs among cancer patients. This study compared healthcare utilization and OOP expenditure between adults with and without cancer in Korea and quantified adjusted differences associated with cancer. Data were obtained from the 2023 Korea Health Panel Survey and included adults aged ≥ 19 years. Healthcare utilization outcomes included outpatient visits, hospitalizations, emergency visits, total health encounters. OOP expenditures included inpatient, outpatient, emergency, pharmacy, and total annual healthcare expenditure. Survey-weighted Poisson or negative binomial regression models and generalized linear models with gamma distribution and log link were used to estimate adjusted differences in healthcare utilization and OOP expenditures associated with cancer status after controlling for sociodemographic, socioeconomic, behavioral, insurance-related, and clinical covariates. Among 10,911 participants, 626 (5.7%) reported a history of cancer and 10,285 (94.3%) had no history of cancer. Mean annual healthcare utilization was significantly higher among participants with cancer than those without cancer including hospitalization (0.78 vs. 0.19), outpatient visits (32.93 vs. 18.59), emergency visits (0.20 vs. 0.11), and total utilization (33.91 vs. 18.89) Cancer was independently associated with an adjusted difference of 8.93 total visits, 0.49 hospitalizations, 8.36 outpatient visits, and 0.08 emergency visits annually (all p < 0.001). OOP expenditure was substantially higher among cancer patients ($1,828 vs. $676; p < 0.001), with significant adjusted differences in total OOP expenditure ($917), inpatient ($639), outpatient ($224), and pharmacy ($53). Lung ($2453), cervical ($1341), colorectal ($1113), and other cancers ($1201) showed the highest expenditure. Cancer is associated with markedly greater healthcare utilization and significant OOP expenditure burden despite Korea's National Health Insurance (NHI) coverage. Strengthening financial protection, expanding coverage for high-cost care, reinforcing OOP caps, and supporting vulnerable households are essential. Future longitudinal studies incorporating cancer stages, treatment pathways, and indirect costs are warranted.
Gastric cancer (GC) remains a leading cause of mortality in Vietnam, where distant metastasis is frequently present at diagnosis. Since accessible biomarkers are scarce, we evaluated the association of Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) with distant metastasis in a Vietnamese cohort to develop a model for patient stratification. This retrospective study analyzed 114 patients, categorizing into metastatic (Stage IV) and non-metastatic groups per AJCC 8th criteria. The optimal cutoffs were determined using receiver operating characteristic (ROC) curve analysis. The diagnostic efficacy between models was compared by DeLong's test. LASSO regression was employed to identify stable indicators. A multivariable logistic regression model was constructed, and its performance was evaluated using 1,000 bootstrap resamples. Clinical utility was assessed via Decision Curve Analysis (DCA). Distant metastasis was 44.7% of cases. Optimal cutoffs of 2.0 for NLR and 181.5 for PLR were identified. Both markers were significantly higher in metastatic group and positively correlated with disease progression. LASSO identified PLR, NLR, and tumor location as the most robust determinants. In multivariable analysis, only multiple tumor location and high PLR remained independent prognostic factors. The combined model integrating clinical factors with NLR and PLR significantly outperformed clinical features alone (AUC: 0.766 vs. 0.619, p=0.0036), with an optimism-corrected C-index of 0.708. At a 0.586 threshold, the model achieved 82.5% specificity and 62.7% sensitivity, supporting a conservative "rule-out" strategy. Calibration slope was 0.659. DCA demonstrated superior net benefit across a 15%-90% risk range; specifically, at a 40% threshold, model spared 19 per 100 patients from unnecessary intervention. This study establishes the first baseline for NLR and PLR in the Vietnamese cohort, showing an association of these biomarkers with GC distant metastasis. A model integrating PLR, NLR and tumor location optimizes patient stratification and resource allocation in resource-constrained healthcare environments. Gastric cancer (stomach cancer) is a leading cause of cancer-related deaths worldwide. In Vietnam, many patients are diagnosed only after the cancer has already spread to distant parts of the body (metastasis). When cancer spreads, it becomes much harder to treat. Doctors need affordable and reliable ways to identify which patients are at a higher risk of metastasis to improve how they manage the disease. Researchers studied 114 gastric cancer patients at the Ho Chi Minh City Oncology Hospital. They looked at two specific markers found in routine, inexpensive blood tests: the Neutrophil-to-Lymphocyte Ratio (NLR) and the Platelet-to-Lymphocyte Ratio (PLR). These markers measure the balance of different white blood cells and platelets, which partially reflect the body’s “inflammation” levels in response to a tumor. The study found that patients with advanced, metastatic cancer had significantly higher NLR and PLR levels compared to those in earlier stages. By combining these blood markers with other clinical information—such as the patient’s and tumor’s data —the researchers created a diagnostic model. This combined model was much more accurate at identifying patients with distant metastasis than using clinical information alone. Because these blood tests are simple, low-cost, and already widely available in hospitals, they offer a practical way for doctors to monitor cancer progression. Using the NLR and PLR ratios can help healthcare providers in Vietnam and elsewhere better identify high-risk patients and personalize their treatment plans more effectively.
Oral cancer is among the ten most common malignancies worldwide and can be highly lethal if not diagnosed and treated promptly. Mapping the spatial and geographic distribution of this cancer can assist health authorities in planning effective prevention, control, and treatment strategies by identifying its geographic and demographic patterns. This study aimed to investigate the demographic characteristics and geographic distribution of oral cancer in Golestan Province, Iran, during the period 2014-2021. This trend study used data from the National Cancer Registry System of Golestan Province, Iran, covering the period from 2014 to 2021. Geographic mapping of the cities in Golestan Province was performed using ArcGIS software. The annual incidence of oral cancer was calculated for each city and expressed as the number of cases per 100,000 population per year. A total of 390 patients with oral cancer were identified in Golestan Province between 2014 and 2021. Of these, 200 (51.3%) were male and 190 (48.7%) were female. The mean age of the patients was 56.18 ± 17.37 years, ranging from 2 to 96 years. The standardized annual incidence rate of oral cancer in Golestan Province ranged from 4.25 to 6.75 cases per 100,000 population during the study period. Among the cities of the Province, Maraveh Tappeh showed the highest incidence rate, with an average incidence of 12.35 cases per 100,000 population. The incidence of oral cancer in Golestan Province demonstrated temporal fluctuations during the study period, with higher rates observed in several northern cities. Geographic mapping of the disease may provide valuable insights into the potential influence of environmental, cultural, and lifestyle factors on the distribution of oral cancer and can support more targeted prevention and control strategies.
Spending on cancer medicines has increased rapidly worldwide, driven by the introduction of immunotherapy and targeted therapy. Australia exemplifies this trend, with cancer medicines representing one of the largest and fastest-growing areas of expenditure for Australia's public medicines funder, the Pharmaceutical Benefits Scheme. While this growth reflects therapeutic innovation and expanded clinical use, it has intensified concerns around the real-world safety, effectiveness, and value of novel therapies once adopted into routine care. Randomised clinical trials remain essential for regulatory approval but often provide limited insight into outcomes in broader, more heterogeneous populations, particularly as many therapies enter practice via accelerated pathways based on surrogate endpoints. Population-based cancer registries offer an important resource for postmarket surveillance when linked with national administrative datasets such as dispensing and hospitalisations records. However, limitations in registries' timeliness, disease stage ascertainment, biomarker and genomic data capture, and information on recurrence and progression constrain their current utility. This perspective examines the Australian population-based cancer registry landscape, highlighting its strengths, untapped potential, and critical gaps. We outline priority enhancements required to realise a robust, whole-of-population cancer medicine surveillance system that can inform clinical practice, policy, and sustainable health care decision making.
Opioid-induced constipation is a practical bowel-management issue when opioids are started for cancer pain, but real-world naldemedine timing and subsequent laxative needs remain variable. To describe naldemedine initiation timing/context after oxycodone start and early additional laxative adjustment among adults with cancer. Single-center retrospective cohort study using routine clinical records. Adults with cancer pain in a single-center Japanese cancer-care setting who started oxycodone between June 1, 2017, and December 31, 2018, and subsequently received naldemedine. Concurrent initiation was naldemedine prescribed as part of the same oxycodone-start prescribing decision; reactive initiation was naldemedine added as a separate prescribing decision after physician-recognized constipation during ongoing oxycodone therapy. The primary outcome was prescription-record-based additional laxative initiation or dose escalation of existing laxatives within 7 days after naldemedine initiation. Secondary outcomes were oxycodone-to-naldemedine interval and diarrhea-related discontinuation within 28 days. Among 101 patients, the primary outcome occurred in 6/31 (19.4%) concurrent and 2/70 (2.9%) reactive cases (p = 0.010). The reactive group had a median oxycodone-to-naldemedine interval of 15 days (interquartile range, 5-83); diarrhea-related discontinuation occurred in 2/31 (6.5%) versus 6/70 (8.6%). Concurrent naldemedine at oxycodone start did not eliminate early additional laxative initiation or escalation. Naldemedine timing should be understood within individualized bowel-management planning, with conventional or rescue laxatives considered when clinically appropriate.
To comprehensively assess the gastric cancer burden in China over the past three decades and analyze its epidemiological trends to inform control strategies. This was a population-based observational study that systematically evaluated the burden of gastric cancer in China from 1990 to 2023, utilizing data from the Global Burden of Disease (GBD) 2023 study. We evaluated gastric cancer burden metrics from GBD 2023, including incidence, mortality, YLLs, YLDs, and DALYs. Joinpoint regression and age-period-cohort modeling were employed to analyze trends and epidemiological characteristics. Between 1990 and 2023, the age-standardized incidence rate decreased from 54.23 to 25.04 per 100,000 , and mortality decreased from 50.93 to 16.62 per 100,000. Joinpoint analysis showed an average annual percentage change of -2.8% in incidence, with a significant trend reversal in females during 2020-2023. Age-period-cohort analysis revealed peak risk at 65-69 years and lower risk in recent birth cohorts. While China has achieved substantial reductions in gastric cancer burden over 34 years, emerging challenges include trend reversals in females and persistent sex disparities, necessitating targeted prevention strategies.
The combination of trastuzumab and chemotherapy, with or without pembrolizumab, is the current first-line standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer and gastroesophageal junction cancer. However, upon disease progression, subsequent therapies often yield limited clinical benefit. The mechanisms of drug resistance to trastuzumab remain unresolved. Current studies on its resistance mechanisms have largely focused on alterations in the HER2 pathway, including HER2 heterogeneity, reduced or absent HER2 expression, variations in HER2 dimerization, and mutations in downstream components, among others. Crucially, as a monoclonal antibody, the antitumor activity of trastuzumab is partially mediated by the immune system, yet the immunology-related mechanisms of resistance are frequently overlooked. In this review, we systematically analyse the outcomes of both successful and failed clinical trials of anti-HER2 agents to propose that immune escape within the tumor microenvironment is a key driver of trastuzumab resistance in HER2-positive gastric cancer.
The growing availability of public genomic repositories led to increased use of integrative and meta-analytic approaches to combine multi-omics datasets for biomarker discovery. Building on this framework, our study applies a molecular discovery approach to identify diagnostic biomarkers for cervical pre-cancer in high-risk HPV-positive women using aggregated genomic evidence across populations. This study performed a secondary analysis of publicly available DNA-methylation datasets identified through a systematic search of the Gene Expression Omnibus database to enable integrative analysis. After employing standard preprocessing methods across the selected DNA-methylation datasets, statistical analyses (specifically limma and meta-analysis with a random-effects model) were used to calculate the cumulative standardized effect sizes for all 9570 genes across the 4 selected studies. This cross-dataset analysis led to the identification of 4 promising, non-population-specific genes, that show potential for detecting precancerous cervical lesions in high-risk HPV-positive women. Collectively, these genes reflect a molecular profile associated with Cervical Intraepithelial Neoplasia lesions undergoing malignant progression. By leveraging aggregated data, our findings enhance the potential of generalization of biomarker signals and illustrate the strength of multi-data sets integration in advancing cervical pre-cancer triage screening strategies. Given their diagnostic promise, further experimental validation in large and diverse cohorts is warranted to evaluate their clinical applicability.
Ovarian cancer remains one of the most lethal gynecological malignancies due to late diagnosis, limited treatment options, and high recurrence rates. Recent evidence highlights the ubiquitin-proteasome system as a key contributor to cancer progression, with ubiquitin-conjugating enzyme E2 J1 (UBE2J1) emerging as a potential oncogenic target. In this study, a comprehensive in silico drug discovery approach was applied to identify natural phytochemicals capable of inhibiting UBE2J1. Sequence and structural modeling confirmed the reliability of the predicted protein conformation, while protein-protein interaction analysis underscored its central role in ubiquitination pathways. Five plant-derived compounds were screened through molecular docking, among which Withaferin A exhibited the strongest binding affinity (- 8.4 kcal/mol), forming stable hydrogen bonds and hydrophobic interactions with key active site residues. Molecular dynamics simulations further demonstrated the stability of the protein-ligand complex, with favorable RMSD, RMSF, and radius of gyration profiles. ADMET and drug-likeness evaluations revealed that Withaferin A complies with Lipinski's rule of five, possesses good intestinal absorption, and shows non-carcinogenic and non-mutagenic properties. Binding free energy calculations using MM/GBSA supported its strong affinity toward UBE2J1. These findings highlight Withaferin A as a promising natural inhibitor of UBE2J1 and provide a foundation for future experimental validation aimed at developing targeted therapies against ovarian cancer.
Surgical innovation in colorectal cancer is increasingly judged not by technical feasibility alone, but by whether it improves oncological outcomes, preserves function, reduces morbidity, or makes difficult procedures more reproducible. This structured narrative review examines major surgical studies published from January 2024 through July 2026, while retaining earlier landmark reports when needed to interpret safety and implementation. The strongest recent randomized evidence concerns robot-assisted rectal cancer surgery. In the REAL trial, robotic surgery improved 3-year locoregional control, disease-free survival, and early functional recovery compared with laparoscopy in middle and low rectal cancer, although overall survival did not differ and generalizability beyond experienced Chinese centers remains uncertain. For transanal total mesorectal excision, noninferiority in the TaLaR trial must be interpreted in light of its -10% margin, the experience of participating centers, and early reports of multifocal local recurrence during implementation. Individual trials of indocyanine green fluorescence angiography have yielded mixed results; however, a 2026 meta-analysis of nine randomized trials found lower leakage rates overall and after left-sided and rectal resections, but not after right-sided colectomy, supporting procedure-specific use. Robotic colectomy is feasible but has not clearly surpassed mature laparoscopy. Intracorporeal anastomosis is associated with faster recovery and greater flexibility in extraction-site selection and may reduce extraction-site hernia, whereas long-term oncological equivalence has not yet been established. Across these fields, benefit appears context-specific and closely linked to case selection, surgeon experience, technical standardization, and structured audit.
In this chapter, we describe a general sample preparation workflow for small extracellular vesicles (sEVs) from breast cancer cell lines using techniques such as protein solubilization, enzymatic digestion, and Fe3+-immobilized metal affinity chromatography (IMAC) and titanium dioxide (TiO2) enrichment prior to mass spectrometry-based proteomic analysis. This workflow can be used to perform global phosphoproteomics of sEVs enabling the study of tumor biology and the discovery of biomarkers for cancer diagnosis and treatment.
Cancer remains a leading cause of mortality worldwide, highlighting the need for therapeutic strategies that reduce systemic toxicity and drug resistance. Resveratrol (RES), a natural polyphenolic stilbenoid, possesses antioxidant, anti-inflammatory, pro-apoptotic, anti-metastatic, and chemosensitizing activities. However, its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolic clearance, and consequently low systemic bioavailability. Nanotechnology-based drug delivery systems provide a promising strategy to address these limitations. This review summarizes recent advances in RES-loaded nanoformulations, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, micelles, inorganic nanocarriers, protein-based systems, and biomimetic vesicles. Their therapeutic performance is evaluated across prostate, lung, colorectal, breast, and other cancers, with attention to tumor targeting, controlled release, combination therapy, multidrug-resistance reversal, and modulation of cancer-relevant pathways such as NF-κB, p53, and PI3K/Akt/mTOR. Current oncology-related clinical evidence for RES is still largely based on conventional oral or micronized formulations. Translation of engineered RES nanocarriers therefore requires stronger evidence on scalable manufacturing, carrier-specific safety, heterogeneous tumor delivery, and biomarker-guided trial design. This review also introduces a semi-quantitative prioritization framework based on model-readiness, translational priority, and safety-alert scoring for future PBPK, PK-PD, nano-QSAR, and machine-learning analyses.
Immune checkpoint inhibitors such as anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies have transformed cancer therapy, but their clinical use is often limited by severe systemic toxicities, particularly with anti-CTLA-4. To address this, we developed Myo-P3, a retrievable hollow-fiber encapsulated cell therapy device containing genetically engineered human myoblasts that secrete low doses of anti-CTLA-4 directly into the tumor microenvironment. In a murine colorectal cancer model, peritumoral implantation of Myo-P3 significantly delayed tumor progression and improved survival versus untreated controls. Treatment induced local immune modulation, with early reductions in intratumoral FoxP3+ regulatory T cells and hCTLA-4+ CD4+ T cells, consistent with CTLA-4 blockade, while maintaining substantially lower systemic antibody levels than systemic ipilimumab. Although this model does not permit comprehensive assessment of long-term secretion or toxicity, these data support the feasibility and biological activity of localized anti-CTLA-4 delivery and highlight a controllable, retrievable platform to reduce systemic exposure.
Tertiary lymphoid structures (TLS) are associated with prognosis in solid tumours. Their value for predicting axillary nodal involvement in oestrogen receptor-positive luminal breast cancer remains uncertain. Three published TLS signatures were scored by single-sample gene set enrichment analysis in oestrogen receptor-positive luminal tumours. The Cancer Genome Atlas Breast Invasive Carcinoma cohort (TCGA-BRCA) included 632 cases, of which 379 met strict consensus. METABRIC included 1086 cases, of which 663 met strict consensus. Logistic models adjusted for age and pathological tumour stage. Strict consensus, majority vote, and continuous scores were compared. Performance assessment included bootstrapped changes in area under the receiver-operating-characteristic curve, Brier scores, calibration, and decision-curve analysis. Survival was evaluated in METABRIC and explored in TCGA-BRCA. Strict-consensus TLS status was not associated with nodal positivity in TCGA-BRCA (adjusted odds ratio: 0.95, 95% confidence interval: 0.62-1.45, P = 0.822). METABRIC was similar (odds ratio: 0.76, 95% confidence interval: 0.55-1.06, P = 0.105). Full-cohort METABRIC analyses detected small majority-vote and continuous-score associations, absent in TCGA-BRCA. Across specifications, bootstrapped changes in area under the receiver-operating-characteristic curve ranged from 0.0002 to 0.0089, with minimal Brier-score improvement and no stable decision-curve benefit. In METABRIC, the univariable overall survival association attenuated after age adjustment (hazard ratio: 1.33-1.10). TCGA-BRCA survival analyses were nonsignificant. TLS transcriptomic signals showed small, cohort-dependent associations with nodal status but no reproducible or clinically meaningful incremental predictive value. These data do not support replacing sentinel lymph node biopsy with a TLS signature in oestrogen receptor-positive luminal breast cancer.
Traditional cancer therapy has limitations due to a lack of specificity and efficiency in tumor-targeting, toxicity issues, and biological barriers, which affect the clinical efficacy of traditional agents as well as synthetically designed carriers. Exosomes have gained popularity as excellent biological carriers owing to their inherent biocompatibility, capability to overcome biological barriers, and ability to transport cargoes between cells naturally. This review discusses how engineering of exosomes, hybrid exosomes, and exosome mimics could be employed to deliver therapies, enhance tumor penetration, and enable multimodal treatment of cancers, including chemotherapy, gene therapy, immunotherapy, and theranostics. The biomimetic and hybrid platforms may overcome key limitations of native exosomes, particularly low production yield, heterogeneity, limited drug-loading efficiency, and scalability constraints, while preserving desirable biological functionality. Moreover, the review also emphasizes that the standardization in manufacturing, reproducibility in cargo, safety evaluation, and regulatory approval are the major obstacles to clinical application. Unlike many earlier reviews that were mainly centered on native exosomes, the current review discusses the engineering aspects of exosome-like nanoplatforms from a translational viewpoint.
[This retracts the article DOI: 10.1016/j.omto.2021.01.013.].
[This retracts the article DOI: 10.1016/j.omtn.2020.08.017.].
[This retracts the article DOI: 10.1016/j.omto.2020.01.003.].
[This retracts the article DOI: 10.1016/j.omto.2021.09.007.].
Colorectal cancer remains a leading cause of cancer-related death, and there is an urgent need for new therapies that can specifically induce tumor cell apoptosis. Plant polyphenols have emerged as promising alternatives for cancer treatment. Flourensia cernua and F. retinophylla are polyphenol-rich plants native to northern Mexico, known for their use in traditional medicine, and recently reported to have anti-inflammatory and antimicrobial properties; however, their anticancer effects remain poorly studied. This study aimed to evaluate the ability of polyphenolic extracts from F. cernua and F. retinophylla to induce apoptosis in HT-29 human colon adenocarcinoma cells in vitro and to explore the mechanisms of cell death triggered by these extracts. Polyphenolic extracts were prepared from dried leaves using ethanol and analyzed for antioxidant activity and polyphenolic composition. HT-29 cells were treated with different concentrations, and cytotoxicity was measured by MTT assay. Apoptosis was analyzed through intrinsic and extrinsic pathways, caspase activity, and detection of apoptosis-related proteins via Western blot and antibody array. Both Flourensia extracts are rich in polyphenols and exhibit high antioxidant capacity. Treatment with the extracts caused dose-dependent growth inhibition of HT-29 cells. F. cernua extract triggered cytochrome c and SMAC release, indicating activation of the intrinsic pathway, and also upregulated death receptor proteins and caspase-8, indicating engagement of the extrinsic pathway. F. retinophylla produced a weaker response, mainly modulating intrinsic-pathway markers. Both extracts also increased caspase-3 levels, consistent with engagement of apoptotic signaling. These findings demonstrate the potential of Flourensia-derived extracts as alternative anticancer agents with apoptosis-inducing potential in human colon adenocarcinoma cells.