Asian Pacific Journal of Cancer Biology

Impact of SLCO1B3 Ser112Ala Genetic Variation on Efficacy and Safety of Paclitaxel in Iraqi Women with Breast Cancer

Wed, 29 Apr 2026 05:08:42 +0000

Objective: This study intended to detect genetic polymorphism in active transporter SLCO1B3 Ser112Ala (rs4149117) and study the effect of this variation on efficacy and safety of paclitaxel in Iraqi women with breast cancer.

Methods: The cross-sectional observational study was involved 150 women with breast cancer who received paclitaxel. These women were assessed individually in the 2nd week of paclitaxel therapy using a questionnaire to obtain demographic data, including age and body mass index, and the probability and severity of paclitaxel’s side effects. At the same time, neutrophilia count and breast cancer markers were assessed.

Result: The wild type (TT) was detected in about 14% of breast cancer cases. While the mutant type (GG) and the heterozygous type (TG) were detected in about 65% and 21% of the cases, respectively. The results did not exhibit a significant difference among Iraqi breast cancer women who carried TT, TG, and GG genotypes regarding breast cancer markers (CA 15.3 and CEA) and paclitaxel related adverse effects (neutropenia, oral mucositis, and peripheral neuropathy) at P > 0.05.

Conclusion: The SLCO1B3 334T>G genotyping was significantly distributed among Iraqi women with breast cancer. Still, there was no significant association between the SLCO1B3 334T>G genetic variation and efficacy and safety of paclitaxel.

Synergistic Cytotoxicity of Newcastle Disease Virus and High-Dose Dimethyl Fumarate in Breast Cancer Cells Is Accompanied by reduction of Selectivity in Normal Cells

Wed, 29 Apr 2026 05:12:43 +0000

Background: Newcastle disease virus (NDV) is a promising oncolytic virus with selective cytotoxicity against cancer cells, while dimethyl fumarate (DMF) is an FDA-approved NF-κB inhibitor showing interesting anticancer activity. The current work assessed the combined cytotoxic effect of NDV and DMF on breast cancer cells and on normal rat embryo fibroblast (REF) cells.

Methods: Killing ability was evaluated using crystal violet cytotoxicity assay following treatment with NDV (MOI 1–5), DMF (15.6–500 µg/mL), or their combinations. Drug interaction was measured using the Chou–Talalay combination index.

Results: NDV alone showed higher cytotoxicity toward breast cancer cells than toward normal REF cells, confirming its known selectivity. DMF demonstrated dose-dependent cytotoxicity in all tested cell lines. Interestingly, combining NDV with medium–high concentrations of DMF produced strong synergistic effects not only in breast cancer cells but also in normal REF cells. This indicates that DMF eliminates the essential cancer-selectivity of NDV and increases normal-cell susceptibility to the combination treatment.

Conclusion: While NDV and DMF display strong synergistic cytotoxicity in vitro, this synergy also induced in normal cells, resulting in a loss of the selective oncolytic nature of NDV. These findings emphasize a major limitation of the combination strategy and highlight the need for dose-optimization studies with lower DMF concentrations or alternative NF-κB inhibitors to preserve selectivity while maintaining anticancer activity.

Integrated Bioinformatics and Experimental Analysis of KIFs in Ovarian Cancer Reveals Mitotic Drivers and Germline Variant Associations

Wed, 29 Apr 2026 05:15:49 +0000

Background: Ovarian cancer is the deadliest gynecologic malignancy, yet its genomic drivers remain incompletely understood.

Methods: We integrated multi-omics data from TCGA-OV (n = 379), GTEx normals (n = 88), and two GEO cohorts (GSE26712, GSE18520) to analyze differential expression, CNV, pathway enrichment, and protein–protein interactions. Germline variants were assessed through eQTL mapping and functional annotation. KIF17 expression and rs13375609 genotypes were experimentally validated using qRT-PCR and T-ARMS PCR in an independent cohort (12 tumors, 10 normals).

Results: We identified ~3,200 dysregulated genes, with mitotic kinesins (KIF11, KIF17, KIF18A, KIF20A) markedly upregulated and frequently amplified. High KIF11 or KIF14 expression correlated with reduced overall survival. GSEA indicated strong enrichment of mitotic spindle and G2/M checkpoint pathways, while PPI analysis identified KIF11 and KIF17 as central mitotic hubs. Two KIF17 variants (rs2297299, rs13375609) showed significant eQTL effects. Experimental validation confirmed elevated KIF17 expression and higher frequency of the rs13375609 A allele in ovarian cancer (27% vs. 11%; p = 0.012; OR = 2.8), with the TA genotype showing an even stronger association (p = 0.004; OR = 4.1).

Conclusions: Multi-omics integration and experimental validation identify KIF11, KIF14, and KIF17 as key mitotic drivers and potential biomarkers in ovarian cancer, with rs13375609 emerging as a promising susceptibility variant.

Serum Omentin-1 Level as a Biomarker in Prostate Cancer

Ali Miqdad Mohammed, Abrar I. Albadr, Haider Jaber Sagban (Author) — Wed, 29 Apr 2026 05:20:31 +0000

Objective: To evaluate serum omentin-1 levels in prostate cancer patients relative to healthy controls and to assess its variation between tumor stages and Gleason score categories.

Methodology: This case-control research involved 176 participants (88 prostate cancer patients and 88 controls) from the National Teaching Oncology Hospital in Najaf, Iraq. Serum omentin-1 concentrations were verified by ELISA tests, and relationships with PSA, BMI were measured. ROC analysis was used to assess diagnostic efficacy.

Results: Omentin-1 levels were markedly elevated in prostate cancer patients (43.4 ± 22.6 ng/mL) compared to controls (26.1 ± 6.6 ng/mL, p < 0.01). ROC analysis showed reasonable diagnostic accuracy (AUC = 0.73).

Conclusion: Serum omentin-1 levels are elevated in prostate cancer, and no significant differences were observed across tumor stages or Gleason score categories, indicating that its elevation does not appear to be stage-dependent in this cohort. Further studies are needed to elucidate the mechanistic role of omentin-1 in prostate carcinogenesis, as well as its diagnostic and prognostic potential.

Functional Impact of Interleukin -33 Polymorphism on IRF8 and TGF-β Regulation in Leukemia Patients

Wed, 29 Apr 2026 05:45:09 +0000

Introduction: The immune system plays an important role in controlling cancer development. Leukemia, a malignant disorder of hematopoietic tissues, is characterized by the abnormal proliferation of white blood cells. Unlike solid tumors, leukemia involves a systemic increase in aberrant blood cells rather than localized masses. This inflammatory condition is driven by immune mechanisms involving pathogenic cytokines, among which Interleukin-33 (IL-33) plays a complex and dual role. IL-33 influences the immune system and the tumor microenvironment (TME), potentially promoting or inhibiting leukemia progression depending on the context. A deeper understanding of its mechanisms could pave the way for innovative treatments targeting the IL-33 axis.

Methods: This study aimed to evaluate specific biochemical, hematological, and molecular markers in patients with leukemia. Conducted from June 1, 2024, to September 1, 2024, the study included 60 Iraqi patients with leukemia and 30 healthy controls. Serum levels of interferon regulatory factor 8 (IRF8) and transforming growth factor-beta (TGF-β) were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Single-nucleotide polymorphisms (SNPs) of the IL-33 gene (rs928413) were assessed using Polymerase Chain Reaction (PCR) with a resistance mutation system.

Results: Revealed a highly significant increase in IRF8 levels in leukemia patients compared to controls (P < 0.0001), suggesting a strong association with the pathological state. While overall TGF-β levels did not differ significantly between groups, analysis of genetic polymorphisms indicated a potential influence of the IL-33 rs928413 genotype on TGF-β regulation in patients. Specifically, the GG genotype was associated with the highest IRF8 and TGF-β levels in patients. Although allele distribution of IL-33 rs928413 did not show a direct association with increased risk in this sample, the findings suggest a complex interplay between IL-33 gene polymorphisms, IRF8, and TGF-β in leukemia.

Conclusion: Leukemia patients exhibit elevated immune markers, particularly IRF8, which may play a significant role in disease onset and progression. Further studies are warranted to elucidate the molecular mechanisms linking IL-33 gene polymorphisms to IRF8 and TGF-β function in leukemia, and to explore their potential as therapeutic targets or prognostic markers.

Immunohistochemical Study of Tissue Expression of Trophoblast Cell Surface Antigen 2 (TROP2) Protein in Prostatic Carcinoma and Benign Hyperplasia

Wed, 29 Apr 2026 05:49:37 +0000

Background: Prostate cancer is the second most common malignancy affecting males. TROP2 is a cell surface marker of embryonic stem cells that has been implicated in development of many cancers.

Objective: This study aimed to investigate the immunohistochemical expression of TROP2 Protein in PCa and BPH tissues and explore TROP2 association with the histopathological parameters of PCa.

Materials and Methods: a cross-sectional analytical study was conducted in the pathology laboratory of Suez Canal University Hospital on thirty PCa and fifteen BPH specimens (n=45). Sample was collected from the archived blocks of BPH and prostatic carcinoma. TROP2 expression was assessed using immunohistochemistry.

Results: TROP2 showed positive membranous staining in prostatic epithelial cells of 100% of PCa & in eleven out of fifteen BPH specimens and the difference between the two groups was statistically significant (p-value >0.001). Moreover, high TROP2 expression was found in nineteen PCa and in only four BPH specimens and the difference between the two groups regarding TROP2 staining intensity was also statistically significant (p-value= 0.005). TROP2 showed positive expression in 100% of specimens showing positive perineural invasion and a statistically significant association was found between both TROP2 staining intensity and perineural invasion (p-value >0.05). In addition, TROP2 showed statistically significant validity in discriminating between PCa and BPH (p-value <0.001).

Conclusions: TROP2 is a sensitive prostatic immunohistochemical marker and its expression in PCa is higher than that in BPH. TROP2 is associated with poor prognostic factors of PCa as perineural invasion.

Association between MICA rs2596542 and MTHFR rs1801133 Polymorphisms with the Risk of Hepatocellular Carcinoma

Wed, 29 Apr 2026 05:53:31 +0000

Background: Hepatocellular carcinoma (HCC) susceptibility is influenced by various risk factors, including viral infections, alcohol consumption, tobacco use, and genetic predisposition. The MICA rs2596542 and MTHFR rs1801133 gene polymorphisms have been implicated in HCC pathophysiology.

Objective: This study aims to evaluate the association between single-nucleotide polymorphisms in MICA rs2596542 and MTHFR rs1801133 and the risk of HCC development.

Methods: A total of 240 participants were enrolled, including 80 individuals with HCC associated with hepatitis C virus (HCV) in Group I, 80 individuals with HCC linked to hepatitis B virus (HBV) in Group II, and 80 age- and gender-matched healthy controls in Group III. Genetic polymorphisms of MICA rs2596542 and MTHFR rs1801133 were identified using real-time polymerase chain reaction analysis. This study is distinct in analyzing these SNPs in a well characterized Egyptian cohort with explicit virus stratified comparisons (HBV vs HCV) and combined genotype–clinical modeling to evaluate both susceptibility and clinical correlates.

Results: A significant increase in the heterozygous CT genotype of MICA rs2596542 and in the T allele frequency was observed in Group II (HCC/HBV) compared to Group III (controls). The MICA CT genotype (rs2596542) was clinically associated with HCC stage and alpha-fetoprotein (AFP) levels. Similarly, the AA and GA genotypes of MTHFR rs1801133 and their mutant A allele frequency were notably elevated in Groups I and II compared to controls. The GA and AA genotypes of MTHFR rs1801133 showed clinical correlations with HCC staging and AFP levels. Multivariate analysis identified hypercalcemia, back pain, metastatic disease, and multiple lesions as independent predictors of survival.

Conclusion: MICA (rs2596542) and MTHFR (rs1801133) polymorphisms were determined to be independent risk factors for HCC disease susceptibility. Notably, they were significantly associated with HCC development. These results indicate that MICA (rs2596542) and MTHFR (rs1801133) could represent valuable markers to recognize individuals who are at a greater probability of developing HCC. The most independent factors affecting survival were hypercalcemia, back pain, metastatic disease, and the occurrence of more than one lesion when multivariate analysis was performed.

Interdependent Patient-Reported Outcome Patterns During Breast Cancer Pharmacotherapy: A Correlation-Based Analysis Using EORTC QLQ-C30 and QLQ-BR23

Henry Sutanto, Merlyna Savitri, Ami Ashariati, Een Hendarsih (Author) — Wed, 29 Apr 2026 06:03:56 +0000

Background: Quality-of-life (QoL) assessment is essential in breast cancer care, yet limited evidence describes how interrelated QoL domains change during pharmacotherapy. This study aimed to evaluate correlations among functional and symptom scales using the EORTC QLQ-C30 and QLQ-BR23, highlighting their ability to reveal multidimensional QoL patterns.

Methods: A prospective observational study was conducted in two second-referral hospitals in Indonesia, enrolling 106 female breast cancer patients. QoL was assessed before and after pharmacotherapy using QLQ-C30 and QLQ-BR23. Changes in scores (Δ) were computed, and interdomain relationships were analyzed using Spearman’s rho.

Results: Physical functioning correlated with role functioning (ρ = 0.55, p <0.001), emotial functioning (ρ = 0.33, p <0.001), and social functioning (ρ = 0.31, p = 0.002). Role and social functioning were likewise correlated (ρ = 0.32, p = 0.001), indicating that improvements across functional domains tended to occur in parallel. Symptom scales showed strong positive clustering, including fatigue with pain (ρ = 0.37, p <0.001), insomnia (ρ = 0.35, p <0.001), and systemic side effects (ρ = 0.48, p <0.001). Functional and symptom domains generally exhibited inverse relationships: physical functioning negatively correlated with fatigue (ρ = –0.40), pain (ρ = –0.43), both p <0.001, and systemic side effects (ρ = –0.26; p = 0.01).

Conclusion: The QLQ-C30 and QLQ-BR23 instruments effectively captured structured, clinically meaningful interdependencies. Functional improvements consistently aligned with symptom reductions, revealing coherent functional–symptom clustering. These findings underscore the sensitivity of QoL vinstruments to detect multidimensional patient-reported changes during breast cancer pharmacotherapy.

Antiproliferative Potential and Immunological Safety of Filopaludina bengalensis Extracts: Morphological and Biochemical Insights

Tue, 12 May 2026 06:49:05 +0000

Background: Mollusc-derived compounds are gaining growing attention as potential pharmaceutical agents and functional food supplements. This study investigated the nutraceutical potential of the freshwater mollusc Filopaludina bengalensis, which is widely distributed in West Bengal, India. The research encompassed species authentication and morphological characterization, along with an evaluation of its anti-inflammatory and anticancer activities, to determine its suitability as a natural source of nutraceutical compounds.

Materials and Methods: Filopaludina bengalensis specimens were collected from freshwater habitats and identified using mitochondrial cytochrome c oxidase subunit 1 (COI) gene barcoding for molecular authentication. Morphometric measurements, including shell length and weight, were recorded. The flesh and extrapallial fluid were processed to obtain molluscan mass (FBM) and fluid (FBF) extracts. Proximate composition (moisture, protein, carbohydrate, lipid, and minerals) was analyzed. The cytotoxic activity of both extracts was evaluated in breast cancer cell lines (MCF-7 and MDA-MB-231) using the MTT assay. Anti-inflammatory activity was assessed by measuring nitric oxide inhibition in LPS-stimulated RAW264.7 macrophages, while oxidative stress and immune toxicity were evaluated through reactive oxygen species and nitrite production assays.

Results: Molecular analysis confirmed the identity of F. bengalensis, validating the reliability of COI barcoding for species-level identification and phylogenetic analysis of freshwater molluscs. The mollusc exhibited an average length of 3.02 cm and weight of 5.57 g, yielding 0.5–1.0 ml of extrapallial fluid. Proximate composition analysis revealed high moisture (68.9%) and protein (50.4%) contents, moderate carbohydrates (33.8%), low lipids (4.3%), and notable mineral levels. Both FBM and FBF extracts showed dose-dependent cytotoxicity against MCF-7 and MDA-MB-231 cell lines, with FBF displaying superior potency (IC50 = 19 µg/ml and 49 µg/ml, respectively) compared to FBM (IC50 = 70.3 µg/ml and 142 µg/ml). In LPS-stimulated macrophages, both extracts significantly inhibited nitrite production, with FBF (IC50 = 49.56 µg/ml) showing stronger anti-inflammatory activity than FBM (IC50 = 77.52 µg/ml). Neither extracts induced nitric oxide or reactive oxygen species production in unstimulated macrophages, indicating low immune toxicity.

Conclusion: The findings demonstrate that Filopaludina bengalensis possesses high nutritional value and exhibits selective anticancer and anti-inflammatory activities, particularly within its extrapallial fluid extract. The favourable safety profile and bioactivity of these extracts suggest their potential as natural nutraceutical candidates. Further studies are needed to isolate and characterize the active compounds and elucidate their mechanisms of action for therapeutic development.

Evaluation of Serum IL‑40 and IL‑41 as Integrated Immunometabolic Biomarkers in Iraqi women with Breast Cancer: A Case – Control Study

Hussein Naeem Abd Ali, Hanaa Addai Ali (Author) — Tue, 12 May 2026 06:53:55 +0000

Background: Breast cancer (BC) is a complex malignancy characterized by the uncontrolled proliferation of the mammary epithelium. Emerging research highlights the pivotal role of novel cytokines in the tumor microenvironment. Specifically, the recently identified immunomodulators, Interleukin-40 (IL-40) and Interleukin-41 (IL-41), have been shown to orchestrate B-cell biology, chronic inflammation, and metabolic homeostasis. These cytokines represent critical mediators that influence the intricate pathological landscape and progression of various malignancies, including breast cancer.

Objective: This study aims to quantify serum IL-40 and IL-41 levels in Iraqi women diagnosed with breast cancer and to evaluate their association with clinic-pathological features, disease staging and explore the potential of these cytokines as robust diagnostic and prognostic biomarkers within the clinical setting.

Materials and Methods: This case-control study involved 180 Iraqi women, aged 45–60 years. The cohort consisted of 90 newly diagnosed breast cancer patients at various clinical stages and 90 age-matched healthy individuals who served as the control group. Venous blood samples were collected from all participants to obtain serum. Serum concentrations of IL-40 and IL-41 were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Additionally, lipid profiles and liver functional enzymes were assessed via spectrophotometric analysis.

Result: The study demonstrated that serum IL-40 and IL-41 levels were significantly elevated in breast cancer patients compared to healthy controls (P < 0.001), with high concentrations persisting across all clinical stages. Furthermore, patients exhibited a distinct pro-inflammatory and metabolic profile characterized by significant dyslipidemia (increased TC, TG, LDL-C, and VLDL-C), hepatic dysfunction (elevated ALT, AST, and ALP), and significantly reduced HDL-C levels (P < 0.05). A strong positive correlation was observed between IL-40 and IL-41 (r = 0.90; P < 0.001). Both cytokines showed significant positive correlations with all measured parameters, except for a negative correlation with HDL-C. ROC curve analysis revealed that IL-40 and IL-41 possess high diagnostic potential, with sensitivities of 92.0% and 74.5%, specificities of 88.5% and 70.0%, and Area Under the Curve (AUC) values of 0.892 and 0.738, respectively (at cut-off values of 107.63 pg/mL and 116.35 pg/mL).

Conclusion: Serum levels of IL-40 and IL-41 are significantly elevated in breast cancer patients compared to healthy controls, demonstrating a robust association with disease stage and severity. These findings strongly suggest that the IL-40 and IL-41 axis serves as a promising panel of non-invasive biomarkers for the early diagnosis and prognostic monitoring of breast cancer.

The Impact of miRNA-34a expression, RETN Genetic Polymorphism and Protein Level on Breast Cancer Progression

Tue, 12 May 2026 07:05:49 +0000

Introduction: Obesity, inflammation, and a variety of malignancies, including breast cancer, are all linked to the adipokine resistin. The goal of this study was to determine if specific polymorphism in the RETN (rs3219175) gene in addition to its level enhance the chance of breast cancer susceptibility and to determine if miRNA -34a expression affect the resisten protein levels and its role in breast cancer progression.

Materials and Methods: This study included 100 participants (50 patients and 50 control groups) ranging in age from 35-70 years. Blood samples were collected from Al-Eluia Hospital for Women’s Care, an Oncology Teaching Hospital, between January and July 2021. For the molecular experiment, DNA was extracted from the whole blood that stored in EDTA tube and genetic analysis for the studied SNP was by taq man method with special prop while for RETN protein levels were quantified by ELISA. While for miRNA -34a expression, the total RNA was extracted from the whole blood for both the patients and control groups with the using of miRNA specific primers and by using specific extraction kit with U6 that were used as internal housekeeping gene.

Results: The results showed that the GG genotype was more common in the control group than in the patients (8.9% vs. 5.3%), and that this relationship is significantly associated with the disease (OR= 0.21, p=0.002), while genotype GA was more common in the control group than in the patients (33.9 percent vs. 32.1 percent, p= 0.922). The genotype AA was found to be more common in patients than in controls (65.5 percent vs. 57.1 percent, respectively) with an etiological factor of (OR= 2.63, p=0.012), indicating a significant departure from Hardy Weinberg suggestion for control and patient groups (χ2= 2.301, 4.103) respectively. Serum RETN levels were significantly higher in patients compared to controls (126.52 ±2.36 vs 62.55 ±0.97, p =0.001).

Conclusion: At the same time, the results showed that expression of miRNA34a gene in patients was downregulated as compared with controls (39.04 vs 37.73) and its reversibly correlate to RETN levels.

Checkpoint Inhibition in Microenvironment of Endometrial Cancer: The Emerging Role of KIR and NKG2A

Zainab W. Abdulkhaleeq Alameer, Wafaa S. Shani (Author) — Wed, 29 Apr 2026 06:07:41 +0000

The most common cancer of the female genital tract in developed nations is endometrial carcinoma (EC). Due in major part to population aging and the rising prevalence of diabetes and obesity, its incidence has grown by more than 132% globally over the last three decades. EC-related mortality has continued to rise even while improvements in early detection and treatment have raised survival rates. In contrast to other cancers like breast cancer, less is known about the immunological landscape of EC. Although T cell-based immunotherapies have revolutionized cancer treatment, certain tumor types and patient populations show limited responsiveness. As a result, the innate immune system in particular, natural killer (NK) cells has drawn more attention as a potential substitute effector in cancer immunotherapy. NK cells are powerful antitumor cytotoxic lymphocytes that are frequently compromised in the tumor microenvironment. These cells are controlled by a balance of activating and inhibitory receptors that recognize the lack of MHC class I molecules. Current treatment approaches block inhibitory receptors or stimulate activating ones in an effort to improve NK cells-mediated anticancer responses. With an emphasis on inhibitory receptors, including killer cell immunoglobulin-like receptors KIR and NKG2A, this review investigates the phenotypic and functional features of NK cells within the TME of EC. Understanding how modulation of KIR and NKG2A signaling can restore NK cells cytotoxicity provides a promising avenue for next-generation immunotherapies in EC.

Hierlungxai: A Hierarchical and Explainable Deep Learning Framework for Ct-Based Lung Cancer Classification

B. Usha Priya, V. Lokeswara Reddy (Author) — Wed, 29 Apr 2026 06:11:36 +0000

Accurate detection of lung cancer (LC) from Computed Tomography (CT) scans plays a crucial role in early diagnosis and effective treatment planning. Despite significant progress in deep learning (DL) based classification, current approaches continue to face challenges such as inconsistent intensity normalization, variable slice resolution, noise artifacts, limited dataset availability, subtle nodule appearance, and complex inter-slice dependencies. To address the identified limitations, this study suggests a new approach HierLungXAI, a comprehensive framework integrating advanced preprocessing, hierarchical feature extraction, and explainable AI techniques. The Advanced Image Standardization and Enhancement Pipeline (AISEP) standardizes intensities, enhances contrast, reduces noise, preserves critical structural details, and augments the dataset to improve model generalization. For feature extraction, the HierEffNet (Hierarchical Efficient-based Network) combines deep hierarchical convolutional modules for local nodule-specific details with a hierarchical attention mechanism to capture global volumetric context across consecutive slices. Extracted features are classified using a Multi-Layer Perceptron (MLP), while Grad-CAM provides visual explanations, highlighting key regions influencing predictions. The proposed framework was evaluated on two benchmark datasets, achieving an accuracy of 99.78% and 99.94%, demonstrating superior performance over existing methods. The proposed integration of AISEP preprocessing, HierEffNet hierarchical feature extraction, MLP classification, and Grad-CAM-based interpretability represents a novel approach that simultaneously enhances sensitivity to small and subtle nodules while effectively modeling inter-slice and global contextual relationships, establishing a robust and transparent framework for clinically reliable LC detection.

Thymoquinone and Pyruvate Metabolism in Cancer-Associated Fibroblasts: Emerging Therapeutic Insights

Wed, 29 Apr 2026 06:16:17 +0000

Overview: Cancer continues to be a major global health burden, with GLOBOCAN 2020 reporting 19.3 million new cases and 10 million deaths. Despite advances in treatment, aggressive cancers especially liver and pancreatic remain difficult to manage. Lifestyle factors such as smoking, alcohol use, obesity, and infections contribute significantly to the rising incidence. Conventional therapies often face limitations due to resistance and late-stage progression. Increasing research now focuses on metabolic vulnerabilities within the tumor microenvironment, particularly the role of cancer-associated fibroblasts (CAFs). Driven by signals like TGF-β, PDGF, and IL-6, CAFs fuel tumor growth through metabolic reprogramming and the Reverse Warburg effect. Pyruvate, a central metabolite in glycolysis, plays a key role in these energy-driven processes.

Methods: A structured search of PubMed and Google Scholar was performed using the keywords cancer, pyruvate pathways, Thymoquinone, Nigella sativa, and cancer-associated fibroblasts. Studies addressing TQ’s anticancer and metabolic effects were reviewed.

Results: Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, possesses antioxidant, anti-inflammatory, and antiproliferative actions. Evidence shows that TQ can influence glycolysis, mitochondrial activity, lactate production, and redox balance. However, studies specifically exploring its effects on pyruvate metabolism in CAFs remain limited. Early observations suggest that TQ may interfere with CAF-mediated metabolic support to tumors.

Conclusion: This review highlights the potential of TQ in targeting cancer metabolism, particularly pyruvate-related pathways in cancer cells and CAFs. Further focused research may help translate these insights into effective metabolic-based therapeutic strategies.