Search Results (2,222)

Immune checkpoint receptors (ICRs) play a pivotal role in modulating antitumor immunity and have become central targets in the immunotherapy of genitourinary (GU) malignancies. This review provides a comprehensive overview of the fundamental mechanisms of ICR signaling, the expression and pathophysiological roles of these receptors in GU cancers (kidney, bladder, prostate, testicular, and penile), and the evolving therapeutic landscape. Key ICRs, including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT, orchestrate complex signaling cascades that can lead to T-cell exhaustion and tumor immune evasion. Their expression varies significantly across GU cancer types, histological subtypes, and tumor stages, influencing prognosis and therapeutic response. Immune checkpoint inhibitors (ICIs) reinvigorate antitumor immunity by disrupting these inhibitory pathways and remodeling the tumor microenvironment (TME); however, resistance mechanisms (primary, adaptive, and acquired) and immune-related adverse events (irAEs) pose significant clinical challenges. Established biomarkers such as PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI)/deficient mismatch repair (dMMR) status guide ICI use, but their predictive power has limitations. Consequently, emerging tissue-based (e.g., immune cell signatures, multiplex IHC/IF, spatial transcriptomics), liquid biopsy-based (e.g., ctDNA, CTCs, exosomes), and imaging-based (radiomics, AI-driven analysis) biomarkers are under active investigation to refine patient selection and monitor treatment efficacy. The therapeutic armamentarium is rapidly expanding with novel ICIs targeting new receptors, bispecific antibodies, and innovative combination strategies involving ICIs with chemotherapy, targeted therapies, radiotherapy, and other immunotherapies. Furthermore, ICIs are increasingly explored in neoadjuvant, adjuvant, and maintenance settings. This review highlights the dynamic progress in understanding ICR biology and its clinical translation, emphasizing the ongoing efforts to develop more personalized and effective immunotherapeutic strategies for patients with genitourinary tumors. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cancer, characterized by frequent metastasis and poor prognosis. Epithelial–mesenchymal transition (EMT) plays a pivotal role in tumor progression. Protocadherin 9 (PCDH9) has emerged as a potential tumor suppressor, but its relationship with EMT markers in ccRCC remains unclear. This study aimed to investigate the expression patterns and prognostic significance of PCDH9, β-catenin (CTNNB1), Snail (SNAI1), and Vimentin (VIM) in ccRCC. Methods: Immunofluorescence analysis was performed on formalin-fixed paraffin-embedded tissue sections from 48 ccRCC patients (31 low-grade, 17 high-grade) and adjacent normal renal cortex. Findings were validated using The Cancer Genome Atlas (TCGA-KIRC) dataset via GEPIA2/GEPIA3 platforms, including differential expression, correlation, and survival analyses. Results:PCDH9 mRNA was significantly downregulated in ccRCC tumors (TCGA-KIRC), while VIM was upregulated at the transcriptomic level. Tissue-level immunofluorescence quantification revealed discordant patterns, highlighting the influence of cellular heterogeneity on bulk protein assessment. The strong positive correlation between PCDH9 and CDH1 observed in normal kidney was completely lost in tumor tissue. Unexpectedly, PCDH9 showed positive correlations with EMT transcription factors (ZEB1, SNAI1) in tumors. In univariate survival analysis, high PCDH9 and CTNNB1 expression were associated with improved overall survival. Multivariate Cox regression revealed endpoint-specific prognostic signatures: VIM independently predicted disease progression, while SNAI1 predicted overall mortality. CTNNB1 was consistently protective across both endpoints. Conclusions: Our findings support a tumor-suppressive role for PCDH9 in ccRCC and reveal disruption of epithelial adhesion molecule co-regulation during tumorigenesis. The identification of endpoint-specific prognostic signatures has implications for patient stratification and suggests that ccRCC exhibits a partial EMT phenotype rather than classical EMT. Full article

Background/Objectives: Sarcomatoid or rhabdoid renal cell carcinoma (sRCC) represents an aggressive dedifferentiated phenotype of RCC associated with high metastatic potential. The histologic composition of metastatic lesions arising from clear cell RCC with sarcomatoid/rhabdoid differentiation (ccRCC/sRCC) and its relationship to the primary tumor remain incompletely characterized. Methods: We retrospectively reviewed patients undergoing nephrectomy for ccRCC/sRCC who had at least one resected metastatic lesion between 2013 and 2025 at a single institution. Primary and metastatic lesions were characterized by the percentage of clear cell versus sarcomatoid/rhabdoid histology. Associations between sarcomatoid/rhabdoid percentage in the primary tumor, metastatic histology, metastatic location, and overall survival were examined. Results: Twenty-six patients with 63 metastases were included. Metastatic histology demonstrated substantial heterogeneity, with 27 lesions (43%) showing pure clear cell histology, 21 (33%) mixed, and 15 (24%) pure sarcomatoid/rhabdoid. Some patients had multiple metastases with differing histology. Increasing sarcomatoid/rhabdoid percentage in the primary was associated with a higher likelihood of sarcomatoid/rhabdoid in metastases (p < 0.001). ROC analysis demonstrated primary tumor sarcomatoid/rhabdoid percentage predicted sarcomatoid/rhabdoid differentiation in metastases (AUC 0.84, 95% CI 0.73–0.95). An optimal cutoff of 10% sarcomatoid/rhabdoid differentiation predicted sarcomatoid/rhabdoid features in metastases. Metastatic histology varied by site, with lymph node metastases more frequently demonstrating clear cell morphology and visceral metastases more commonly exhibiting sarcomatoid/rhabdoid features. Conclusions: Metastases arising from ccRCC with sarcomatoid/rhabdoid differentiation exhibit marked histologic heterogeneity. These findings highlight the complex biology of ccRCC/sRCC metastasis and underscore the need for studies examining molecular drivers of metastatic heterogeneity, as well as the relationship between metastatic histology and therapeutic response. Full article

Background: Aspirin, initially recognized for its anti-inflammatory, antipyretic and analgesic properties, holds a prominent role in the treatment of cardiovascular disease. The utility of aspirin in cancer therapeutics has been explored and stratified into COX-dependent and -independent mechanisms. COX2 gene expression has been demonstrated to be significantly upregulated in colorectal cancer and various other gastrointestinal malignancies including pancreatic, esophageal, and gastric cancer. This study investigates the relationship of aspirin use and outcomes in patients with colorectal cancer. Methods: The Nationwide Inpatient Sample (NIS) database from 2017 to 2022 was analyzed for patients age > 18 who were hospitalized for colorectal cancer and its decompensations using ICD-10 diagnostic codes. These patients were further stratified based on the long-term use of aspirin. The principal outcome of this investigation are the odds of in-hospital mortality, with secondary outcomes including odds of pulmonary embolism, portal vein thrombosis, acute kidney injury, septic shock, requiring an ICU level of care and odds of hepatic, pulmonary, gastrointestinal and peritoneal or retroperitoneal metastatic disease. Multivariate logistic regression accounting for hospital and patient characteristics was implemented for analysis, with the Charlson Comorbidity Index used to adjust for coexisting comorbidity burden; a p-value (p) of <0.05 was considered statistically significant. Results: In our analysis of the NIS, 596,160 patients were identified with colorectal cancer and 11.7% (69,750) of this population were identified with long-term use of aspirin. Aspirin use was identified to have a significantly reduced odds of in-patient mortality (adjusted odds ratio) [aOR] 0.530, p value < 0.001 95% CI (confidence interval): 0.460–0.617. Patients with aspirin use also demonstrated significantly reduced odds of adverse outcomes and gastrointestinal, hepatic, pulmonary and retroperitoneal/peritoneal metastasis; (aOR 0.606, 95% CI: 0.564–0.653, p < 0.001), (aOR 0.628, 95% CI: 0.582–0.678, p < 0.001), (aOR 0.676, 95% CI: 0.605–0.755, p < 0.001) and (aOR 0.751, 95% CI: 0.685–0.825, p < 0.001) respectively. Conclusions: In recent years, there has been an alarming increase in incidence of colorectal cancer, particularly amongst younger individuals with increased associated mortality. This mortality increase, albeit alarming, is a driving force for treatment innovation with continual examination of our repertoire of medications for possible repurposed applications. COX2-mediated signaling serves as a key promotor of tumorigenic molecular signaling that directly contributes to tumor cell proliferation, angiogenesis and metastasis in colorectal cancer. Aspirin use and its inhibitory action on COX2 demonstrated a significantly reduced odds of in-hospital mortality. Aspirin use is also associated with significantly reduced odds of developing metastatic disease to the liver, gastrointestinal system, lungs and peritoneum in patients with colorectal cancer. These findings convey that aspirin use reduces the likelihood of in-hospital mortality, major comorbid conditions and of developing metastatic disease as compared to those who do not use aspirin. Full article

Background: Platinum-based chemotherapy, including cisplatin and carboplatin, is widely used to treat various cancers, including ovarian cancer. However, its clinical application is limited by dose-limiting toxicities and resistance, with a poor 5-year overall survival rate for ovarian cancer (35–40%). In this study, we used ionisable lipids and developed pH-responsive lipid nanoparticles (LNPs) to address platinum-resistance in ovarian carcinoma. Methods: Cisplatin was loaded into three LNP systems containing monoolein (MO) and synthetic cationic ionisable lipids (OE-Mo, OA-Py, and OA-Pi) dispersed in Pluronic F-127 with 0.9% NaCl. Cisplatin-loaded LNPs (Cis-OE-Mo-NP, Cis-OA-Py-NP, and Cis-OA-Pi-NP) were characterised for size, zeta potential, and internal mesophase structure. Encapsulation efficiencies were determined via HPLC after removing free drug by ultrafiltration. In vivo efficacy was tested using cisplatin-resistant human patient-derived xenograft (PDX) models. Results: The LNPs were well dispersed with particle size of 219–250 nm and a drug loading of ~1.2 mg/mL. Encapsulation efficiencies were 62%, 59%, and 64%, for Cis-OE-Mo-NP, Cis-OA-Py-NP, and Cis-OA-Pi-NP, respectively. Small angle X-ray scattering (SAXS) results showed that the LNPs are pH responsive with structural transitions from a cubic to a hexagonal phase at an acidic pH. Among the tested formulations, Cis-OA-Py-NP resulted in the most significant reduction in tumour volume by ~60% compared to treatment with cisplatin alone. However, they also showed significant toxicity, including >10% weight loss and gross lung and kidney damage, as confirmed by histology. Conclusions: These findings highlight the potential of Cis-OA-Py-NP in reducing tumour volume but underscore the need for further optimisation to improve safety and therapeutic applicability. Full article

The convergence of artificial intelligence and robotic surgery is redefining the management of genitourinary cancers by enhancing diagnostic accuracy, surgical precision, and training efficiency. This narrative review explores recent advancements in artificial intelligence applications across the cancer care continuum, with a focus on prostate, kidney, and bladder malignancies. Artificial intelligence tools, particularly those based on machine learning and deep learning, have demonstrated strong performance in analyzing imaging data, segmenting tumors, predicting pathological features, and supporting clinical decision-making. Intraoperatively, artificial intelligence enables skill assessment, personalized feedback, and real-time navigation by processing data from surgical videos and robotic system sensors. Augmented reality and intraoperative modeling further enhance visualization and margin control during complex procedures. The review also discusses emerging technologies such as single-port robotic platforms, which offer advantages in confined anatomical spaces and support less invasive approaches. Additionally, the growing field of telesurgery is addressed, highlighting its feasibility for complex urologic operations across vast distances. While many of these innovations are still in early stages of clinical validation, their integration into practice has the potential to improve oncologic and functional outcomes, expand access to expert care, and foster the development of next-generation surgical strategies in urologic oncology. Full article

Background: Iodinated contrast media are essential for oncologic imaging but raise specific safety concerns because cancer patients are often exposed to repeated contrast-enhanced computed tomography, nephrotoxic drugs, immune-modulating therapies, and, in selected cases, radioiodine-dependent diagnostic or therapeutic pathways. Methods: We performed a narrative review based on an exploratory search followed by a focused search targeting iodinated contrast use in oncology-related settings. Studies were included if they addressed renal risk and post-contrast acute kidney injury, hypersensitivity and acute adverse reactions, or thyroid dysfunction with radioiodine-related implications. We also considered clinically relevant studies on drug interactions, isotope studies, and laboratory confounding. Results: The evidence base was methodologically heterogeneous, with renal safety as the predominant domain. Kidney injury after contrast-enhanced imaging in cancer patients appeared frequently multifactorial, supporting the broader concept of post-contrast acute kidney injury rather than automatic attribution to contrast alone. Hypersensitivity reactions to modern nonionic iodinated contrast media were generally uncommon, with severe reactions rare, although immune-modulating therapies may alter risk. Thyroid-related effects were usually transient but relevant in patients with thyroid autonomy and in differentiated thyroid carcinoma, where contrast exposure may affect scintigraphy and radioiodine planning. Conclusions: In oncology, iodinated contrast use requires individualized, field-specific risk stratification instead of reflexive avoidance. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, providing substantial survival benefits across a wide range of malignancies. However, ICI-associated renal toxicity encompasses a broad spectrum of clinical entities, ranging from nonspecific acute kidney injury to well-defined immune-mediated nephropathies with distinct pathophysiological mechanisms. Methods: We performed a large-scale pharmacovigilance study using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate immune-mediated nephropathy associated with ICIs from January 2014 to March 2025. To improve specificity and minimize misclassification, the analysis was restricted to well-defined immune-mediated renal adverse events identified using MedDRA Preferred Terms, excluding nonspecific acute kidney injury. Disproportionality analysis was conducted using reporting odds ratios (RORs) with 95% confidence intervals (CIs) to assess associations between individual ICIs, treatment regimens, and nephropathy reporting. Results: Among 203,652 ICI-related adverse event reports (irAEs), 2361 (1.12%) involved immune-mediated nephropathy. Compared with other irAEs (non-nephropathy), immune-mediated nephropathy was more frequently reported in patients aged ≥ 65 years and in those with lung and genitourinary malignancies. Tubulointerstitial nephritis was the predominant subtype. Higher reporting signals were observed with cemiplimab and pembrolizumab, whereas durvalumab and atezolizumab demonstrated lower reporting signals. Combination regimens involving PD-1 and CTLA-4 inhibitors were associated with higher reporting frequencies compared with monotherapy. Conclusions: This real-world pharmacovigilance analysis identifies clinically relevant differences in immune-mediated nephropathy reporting across ICI classes and treatment strategies. PD-1 inhibitors and PD-1/CTLA-4 combination regimens were associated with higher reporting signals, suggesting potential variation in renal safety profiles. These findings should be interpreted cautiously, given the inherent limitations of spontaneous reporting systems, but they provide hypothesis-generating evidence to support future prospective studies with detailed clinical and histopathological correlation. Full article

Cervical cancer constitutes a major global health burden with a high incidence rate. Despite its well-established role in genome stability and cell cycle regulation, its specific anti-tumor mechanism involving the induction of a senescence-like state remains unclear. To determine whether Mg²⁺ impedes cervical cancer progression through the induction of a senescence-like phenotype via the ATM/CHK2/p21 pathway, HeLa cells were used in this study. Cell proliferation, migration, and invasion were measured using CCK-8, EdU, wound-healing, and Transwell assays, while SA-β-gal staining and western blotting served to examine both senescence-related markers and pathway protein expression. A BALB/c nude mouse xenograft model was established to evaluate tumor growth and safety following intratumoral Mg²⁺ injection. The results showed that Mg²⁺ inhibited proliferation, migration, and invasion in a concentration-dependent manner. Treatment with 20 mM Mg²⁺ increased SA-β-gal positivity, decreased Lamin B1 expression, and activated the ATM/CHK2/p21 pathway; moreover, this upregulation of p21 was reversed by an ATM inhibitor. ELISA revealed that 10 mM Mg²⁺ enhanced IL-6 and TNF-α secretion, confirming effective induction of the senescence-associated secretory phenotype, while higher concentrations diminished this effect, which may be partly attributed to the reduction in cell viability. In vivo experiments showed that Mg²⁺ inhibited tumor growth without notable alterations in body weight, liver and kidney function, or serum magnesium levels. In summary, the localized high concentration of magnesium ions induces cells to enter a senescence-like state via the ATM/CHK2/p21 pathway, thereby selectively suppressing malignant cellular behaviors. Notably, its in vivo efficacy and safety profile in vivo are favorable. It is also worth noting that these findings should be interpreted within the context of a preclinical, high-dose local Mg²⁺ model. Full article

This manuscript examines the total toxic releases from electric utilities and mining facilities in the United States in 2020, focusing on their relationships with human health outcomes. The research highlights the adverse effects of air and water pollution, linking exposure to toxic emissions to several health issues, such as low birth weight, respiratory and cardiovascular diseases, and cancers. It underscores the disproportionate impact of these pollutants on low-income and minority populations. This research project utilizes two sets of data: (1) environmental data, the EPA’s Toxic Release Inventory (TRI) data that records total emissions of all-electric and mining facilities, and (2) health data, the PLACES health data. The results of this study show that census tracts exposed to higher toxic releases are expected to have worse health outcomes. The coefficients for total toxic release indicate that higher toxic release corresponds to a higher rate of cancer, chronic obstructive pulmonary disease (COPD), diabetes, kidney diseases, arthritis, cardiac heart disorders (CHD), and stroke. Except for diabetes and kidney diseases, the associations are statistically significant. The analysis indicates the need for comprehensive public health strategies to mitigate the risks posed by toxic releases, particularly for vulnerable communities. Full article

Background: Cancer cells exhibit metabolic reprogramming characterized by increased dependence on glutamine to sustain rapid proliferation and biosynthetic demands. Kidney-type glutaminase (KGA), which catalyzes the first and rate-limiting step of glutamine metabolism, represents a promising therapeutic target, particularly in triple-negative breast cancer (TNBC), an aggressive sub-type lacking effective targeted therapies. This study evaluated 2-amino-4-boronobutyric acid (ABBA), a boronic acid-containing glutamine analog, as a potential KGA inhibitor with anticancer activity. Methods: KGA inhibition was assessed using a fluorometric enzymatic assay. Cytotoxic effects were examined in multiple TNBC cell lines. Covalent docking and molecular simulation analysis were performed to characterize interactions between ABBA and the KGA active site. Results: ABBA potently inhibited KGA activity, with an IC₅₀ of approximately 1.0 μM, demonstrating greater efficacy than several non-proteinogenic amino acid analogs. ABBA induced dose-dependent cytotoxicity across multiple TNBC cell lines, with pronounced sensitivity observed in basal sub-type cells and cellular sensitivity correlated with KGA expression levels. Expression of γ-glutamyl transpeptidase 1 (GGT1) was negligible, and, excluding any off-target effects, the observed anticancer effects are primarily attributed to KGA inhibition. Docking analysis indicated that ABBA forms a reversible covalent adduct with the catalytic Ser286 residue of KGA in a boronate tetrahedral geometry resembling transition-state mimics, while molecular simulation demonstrated stabilization of the complex through hydrogen bonding and electrostatic interactions. Conclusions: ABBA is a potent boron-based glutaminase inhibitor with therapeutic potential for targeting glutamine metabolism in TNBC. Further structural optimization and in vivo evaluation are warranted to advance ABBA toward therapeutic development. Full article

Background/Objectives: Surgical refinements in robot-assisted partial nephrectomy (RAPN) aim to reduce morbidity and optimize renal function preservation, particularly in patients with high-complexity renal tumours. This study describes the no-touch adaptive technique for RAPN and compares its perioperative outcomes, postoperative complications, and resulting early renal function with those of the conventional approach. Methods: A cohort of 72 consecutive patients with high-complexity renal tumours undergoing RAPN was evaluated. The study group included 38 patients treated with the no-touch adaptive technique, while 34 patients underwent the conventional approach. The no-touch adaptive technique consisted of sutureless, off-clamp, simple tumour enucleation with incremental haemostasis and the option to shift to arterial clamping, tumour enucleoresection, or renorrhaphy as needed. The conventional technique involved on-clamp minimal enucleoresection with double-layer renorrhaphy. Outcomes assessed included completion of a fully no-touch procedure, perioperative metrics, 90-day postoperative complications, and 3-month renal function change from baseline. Results: Baseline characteristics were comparable between groups. A fully no-touch RAPN was achieved in 30/38 (79%) patients. Adaptations were required in eight cases: shift to main arterial clamping (n = 2), renorrhaphy (n = 5), or both (n = 1), with one conversion to total nephrectomy due to intractable bleeding. Estimated blood loss was similar between groups (study: 150 mL [IQR 75–250] vs. control: 180 mL [IQR 100–400]). Length of stay was significantly shorter in the study group (3 days [IQR 3–4]) compared with controls (5 days [IQR 6–8]). Any-grade 90-day complications were significantly lower with the no-touch technique (21% vs. 56%, p < 0.01). Clinically significant 3-month eGFR decline occurred in 14% of controls versus 0% of study patients (p = 0.02). Conclusions: The no-touch adaptive RAPN technique is feasible in high-complexity renal tumours and provides reduced morbidity and superior early renal function preservation compared with the conventional approach. Full article

Objective: The existing work was designed to appraise whether Secukinumab diminishes acute kidney injury in a Cisplatin- induced rat model and to explore the potential underlying mechanisms for this protective effect. Methods: In vivo study, rats were distributed haphazardly into five sets (six animals in each group): control, Secukinumab control, Cisplatin (8 mg/kg, a single dose, intraperitoneally (IP)), and two pretreated groups; Secukinumab (10 and 20 mg/kg single subcutaneous (SC) injection) + Cisplatin. Blood samples and kidney tissues were gathered and analyzed histopathologically and biochemically. In vitro investigation, MCF-7 human breast cancer cells were treated with Cisplatin alone with Secukinumab, and cell viability (MTT assay), combination index, and apoptosis-related markers were analyzed. Results: Secukinumab administration lowered serum levels of BUN, creatinine and LDH with marked elevation in renal TAC and a significant reduction in MDA, iNOS, KIM-1 and NGAL compared to Cisplatin. Additionally, Secukinumab pre-treatment markedly suppressed the inflammatory process and enhanced autophagy, reflected by elevated AMPKα1, SIRT1, and Beclin-1, accompanied by reduced P38 MAPK and NF-κB p65 (Phospho-Ser536) levels and expression levels of IL-6 and P62/SQSTM1 in kidney tissues, contrasted with the Cisplatin group. Secukinumab administration effectively protected against kidney injury, and histopathological examinations of the kidneys confirmed these results. On the other hand, in vitro study results revealed that the combination of Cisplatin and Secukinumab had a synergistic cytotoxic effect and an enhancing effect on the apoptotic pathway (increased P53 and BAX and decreased BCL-2). Secukinumab effectively protects against Cisplatin- induced acute kidney injury by decreasing oxidative stress, inflammation, and enhancing autophagy. Additionally, it synergizes with Cisplatin in vitro to promote cancer cell apoptosis, highlighting its dual reno-protective and anticancer potential. Full article

Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet because of its presence in nearly all food types, including potatoes, vegetables, cereals, grains, legumes, shellfish, and organ meat. Cd has no physiological role or nutritional value in the body and causes toxicity to multiple tissues and organs via oxidative stress and chronic inflammation; as such, at high prevalence, it is frequently associated with diseases, notably cancer, heart disease, diabetes, osteoporosis, and chronic kidney disease. Using kidneys and bones as critical toxicity targets, current dietary Cd exposure guidelines vary from 0.21 to 0.83 μg/kg b.w./d. There is a widespread concern about these guidelines because they were based on the excretion of β₂-microglobulin (β₂M) at a rate of 300 µg/g of creatinine as an endpoint. Concerningly, rice is a staple food for over 50% of the world’s population; however, the permissible Cd level in this commodity has not been adequately addressed. This narrative review focuses on critiquing existing food standards and exposure guidelines for Cd. It discusses the threshold-based risk assessment that was used to define the no-observed-adverse-effect level (NOAEL) for Cd, when β₂M excretion was used with Cd excretion at a rate of 5.24 µg/g of creatinine being a threshold. The estimated glomerular filtration rate (eGFR) is recommended as an appropriate kidney disease endpoint. The current view around how Cd uses various transport proteins to enter and induce toxicity to its target cells are summarized. The strategies to minimize Cd accumulation and mitigate its nephrotoxicity are highlighted. Full article

Halogenated polycyclic aromatic hydrocarbons (HPAHs) are persistent contaminants with elevated toxicity, yet dietary exposure data remain limited. Here, we systematically assessed dietary HPAHs using 87 duplicate diet samples collected from populations living in and around a coking industrial area by applying the duplicate diet method, a gold-standard approach that provides precise individual-level exposure information. Thirty-one HPAHs were detected, including seven previously unreported congeners, with mean concentrations of 62.51, 33.68, and 16.52 ng/g in the coking plant, nearby residential, and control areas, respectively. Lipid-rich foods, particularly meats, exhibited the highest HPAH burdens, and thermal processing approximately doubled concentrations in meals collected from the coking plant area. Dietary cancer risk was evaluated using a toxicity equivalency-based incremental lifetime cancer risk (ILCR) framework. Although several HPAHs occurred at low concentrations, congeners with high relative effect potency contributed disproportionately to cumulative cancer risk. Population-level risk distributions revealed that 25.8% of dietary samples exceeded the benchmark ILCR threshold of 10⁻⁴ in the coking plant area. In silico toxicity predictions further indicated potential organ-specific toxicological relevance for the blood, liver, kidney, and cardiovascular systems, supporting the health relevance of dietary HPAH exposure. In general, these results suggest that industrial influence, food composition, and cooking practices jointly contribute to dietary HPAH exposure and toxicity-weighted cancer risk. Our findings highlight the importance of incorporating halogenated congeners into routine monitoring programs and health risk assessments in industrialized regions. Full article