Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global public health and economic burden worldwide in the past few decades. Epidemiological studies have shown that MASLD is a multisystem disease that is associated not only with liver-related complications but also with an increased risk of developing extrahepatic cancers. MASLD is a sexually dimorphic disease with sex hormones playing an important role in the development and progression of MASLD, especially by the levels and ratios of circulating estrogens and androgens. MASLD is associated with hormone-sensitive cancers including breast and gynecological cancer. The risk of breast and gynecological cancer is elevated in individuals with MASLD driven by shared metabolic risk factors including obesity and insulin resistance. Multiple potential mechanisms underline these associations including metabolic dysfunction, gut dysbiosis, chronic inflammation and dysregulated release of hepatokines. However, the effect of hormone therapy including hormone replacement therapy and anti-estrogen treatment on MASLD and female-specific cancers remains debatable at this time. This synopsis will review the associations between MASLD and breast and gynecological cancer, their underlying mechanisms, implications of hormonal therapies, and their future directions.

Evidence has shown that ibuprofen and celecoxib are effective in improving depressive symptoms, but their mechanisms of action are unclear. In this study, we aimed to determine the relationship between these two drugs and depressive disorder (DD) and elucidate potential mechanisms of action.

Relevant targets for ibuprofen, celecoxib, and DD were obtained and screened from multiple online drug and disease public databases. A protein-protein interaction network was obtained. The Centiscape and CytoHubba plug-ins were applied to screen for core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking was performed to predict the binding of ibuprofen and celecoxib to core targets. Examined the differences in core target protein expression between DD patients (DDs, n = 18) and healthy controls (HCs, n = 16) as a further experimental validation of the network pharmacology results.

In total, 220 potential targets for ibuprofen and 316 potential targets for celecoxib were identified and associated with DD. The antidepressant effects of both drugs involve many key targets in pathways such as "pathways in cancer" and "neuroactive ligand-receptor interaction," including ALB, BCL2, MAPK3, SRC, STAT3, EGFR, and PPARG. The binding affinity of ALB with ibuprofen is the strongest, and it is connected only by hydrophobic interactions. Celecoxib exhibits higher affinity at multiple targets such as SRC, EGFR, and PPARG, with stronger and more specific intermolecular interactions, including salt bridges and halogen bonds. Clinical trials have found that serum ALB expression in DDs is significantly lower than that in HCs (t = 6.653, p < 0.001), further confirming the potential role of ibuprofen in DD.

Ibuprofen and celecoxib primarily exert their antidepressant effects through targets and pathways related to inflammation, neural signaling, and cancer, with celecoxib showing a stronger potential antidepressant effect. The expression difference of the core target ALB between depression and healthy individuals further supports the potential effect of the drug on DD. Our findings propose new treatment strategies, support the link between inflammation and depression, and encourage reassessing existing medications for depression.

It has been proposed that more aggressive tumors trigger a stronger inflammatory response than less aggressive types. We hypothesize that systemic immune-inflammatory index (SII) is associated with occult nodal disease (OND) in clinically node-negative patients undergoing lung resection for non-small cell lung cancer (NSCLC).

The study included patients who underwent lung resection with nodal dissection, according to current guidelines, at a single center between 2010 and 2021 for NSCLC. Preoperative SII within 3 weeks of surgery was calculated. OND was defined as a clinically node-negative patient found to be pathologically node-positive. Cut-point analysis for SII was performed to identify the level most strongly associated with OND. Univariable and multivariable logistic regressions were used to examine the association between SII, clinical factors, and OND.

A total of 199 patients met inclusion criteria, of whom 51% (102 of 199) were women. The median number of nodes and nodal stations examined was 13 (interquartile range 9 to 17) and 6 (interquartile range 5 to 6), respectively. The cut point was determined to be SII 112 or more. On univariable analysis, high SII was associated with OND (odds ratio 15.75, 95% CI 2.09 to 118.73, p = 0.007). On multivariable analysis, after controlling for age, BMI, approach, sex, smoking history (pack-years), forced expiratory volume in 1 second, performance status, comorbidity, histology, lymphovascular invasion, tumor differentiation, and tumor size, high SII was associated with OND (odds ratio 34.59, 95% CI 2.69 to 444.88, p = 0.007).

Increased SII is associated with OND in patients undergoing lung resection for NSCLC.

To explore the association of remnant cholesterol (RC) and lipoprotein-associated phospholipase A2 (Lp-PLA2) with composite adverse events in a large-scale prospective study.

All data were collected from the Asymptomatic Polyvascular Abnormalities Community study between 2010 and 2022. Serum cholesterol levels and Lp-PLA2 were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their RC and Lp-PLA2 levels: low-RC/Lp-PLA2-, high-RC/Lp-PLA2-, low-RC/Lp-PLA2+ and high-RC/Lp-PLA2+. The composite endpoint was a combination of first-ever stroke, myocardial infarction or all-cause mortality. Cox regression analyses were performed to evaluate associations of RC and Lp-PLA2 with composite adverse events.

Of the 1864 eligible participants, the average age was 60.6 years, and 74.3% were male. Over a follow-up of 12 years, we identified 500 composite adverse events, including 210 major adverse cardiovascular events and 342 all-cause deaths. When compared with the group of low-RC/Lp-PLA2-, the hazard ratios with 95% confidence intervals in the group of high-RC/Lp-PLA2+ for stroke, myocardial infarction, major adverse cardiovascular event, all-cause death and composite endpoints were 1.37 (0.87-2.16), 0.72 (0.28-1.82), 1.29 (0.85-1.95), 1.61 (1.10-2.38) and 1.43 (1.07-1.91), respectively. A significant interaction between RC and Lp-PLA2 status has been found for all-cause death and composite endpoint (p for interaction <0.05). In addition, joint association of RC and Lp-PLA2 with all-cause death was modified by sex and age of <60 versus ≥60 years (p for interaction: 0.035 and 0.01, respectively).

Elevated RC and Lp-PLA2 levels were associated with an increased risk of composite adverse events, with these associations significantly influenced by sex and age. Our study highlights the synergistic effect of RC and Lp-PLA2 on the composite adverse events.

The very prevalent nature, genetic variability, and intricate tumor microenvironment (TUME) of colorectal cancer (COREC) are its defining features. In order to better understand the molecular and cellular make-up of COREC, this work used single-cell RNA sequencing (SRNAS) to isolate and characterize important cell types as well as their interactions within the TUME. Our analysis of 51,204 cells yielded six distinct types: epithelial, fibroblast, endothelial, T&NK, B, and myeloid. C3 B cells were shown to be the most active in immunological regulation, according to chemokine signaling study, which was one of seven clusters of B cells that were thoroughly subtyped. The examination of copy number variation (CONUV) revealed a great deal of genetic variability, especially in epithelial cells. We traced the activity of three key transcription factor clusters (M1, M2, and M3) across all B cell subtypes using transcription factor analysis. We created a predictive model that correctly sorts patients according to survival results by using marker genes from C3 B cells. In addition, the relationship between genetic changes and the immune system was better understood by tumor mutational burden (TUMUB) and immune infiltration studies. Our research sheds light on the genetic complexity and cellular variety of COREC, which in turn opens up new possibilities for targeted treatments and individualized approaches to patient care.

To develop a deep learning-based method for robust and rapid estimation of the fatty acid composition (FAC) in mammary adipose tissue.

A physics-based unsupervised deep learning network for estimation of fatty acid composition-network (FAC-Net) is proposed to estimate the number of double bonds and number of methylene-interrupted double bonds from multi-echo bipolar gradient-echo data, which are subsequently converted to saturated, mono-unsaturated, and poly-unsaturated fatty acids. The loss function was based on a 10 fat peak signal model. The proposed network was tested with a phantom containing eight oils with different FAC and on post-menopausal women scanned using a whole-body 3T MRI system between February 2022 and January 2024. The post-menopausal women included a control group (n = 8) with average risk for breast cancer and a cancer group (n = 7) with biopsy-proven breast cancer.

The FAC values of eight oils in the phantom showed strong correlations between the measured and reference values (R2 > 0.9 except chain length). The FAC values measured from scan and rescan data of the control group showed no significant difference between the two scans. The FAC measurements of the cancer group conducted before contrast and after contrast showed a significant difference in saturated fatty acid and mono-unsaturated fatty acid. The cancer group has higher saturated fatty acid than the control group, although not statistically significant.

The results in this study suggest that the proposed FAC-Net can be used to measure the FAC of mammary adipose tissue from gradient-echo MRI data of the breast.

Approximately 50% of strokes in patients with cancer are classified as cryptogenic after standard evaluation. Atrial cardiopathy could explain some cancer-related cryptogenic strokes. However, the relationship between cancer and atrial cardiopathy is uncertain.

We conducted a post hoc cross-sectional analysis of baseline data collected from participants enrolled in ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke), a clinical trial conducted from 2018 to 2023 at 185 sites. The analytical cohort presented herein included patients age ≥45 years with cryptogenic ischemic stroke within the past 180 days, of whom a subset had atrial cardiopathy and were randomized into the trial. Atrial fibrillation before enrollment was exclusionary. Linear regression models examined the associations between history of cancer and the atrial cardiopathy biomarkers analyzed in ARCADIA: serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), P-wave terminal force in ECG lead V1, and left atrial diameter index on echocardiogram. Among 3745 patients with cryptogenic stroke, 506 (13.5%) had history of cancer. History of cancer was associated with higher median values of NT-proBNP (126 versus 103 pg/mL, P<0.001) and left atrial diameter index (1.9 versus 1.8 cm/m2, P<0.001) but similar median values of P-wave terminal force in ECG lead V1 (3000 versus 3025, P=0.08). After adjusting for demographics, tobacco use, and body mass index, no significant association remained between history of cancer and log-transformed NT-proBNP (standardized β $$ \beta $$ , -0.06 [95% CI, -0.15 to 0.02]), P-wave terminal force in ECG lead V1 (standardized β $$ \beta $$ , -0.02 [95% CI, -0.11 to 0.08]), or left atrial diameter index (standardized β $$ \beta $$ , 0.06 [95% CI, -0.05 to 0.16]).

In a multicenter, prospective, cryptogenic stroke cohort, history of cancer was not associated with selected biomarkers for atrial cardiopathy.

URL: https://www.ClinicalTrials.gov; Unique Identifier: NCT03192215.

The vasculature plays a critical role in homeostasis and health as well as in the development and progression of a wide range of diseases, including cancer, cardiovascular diseases, metabolic diseases (and their complications), chronic inflammatory diseases, ophthalmic diseases, and neurodegenerative diseases. As such, the growth of the vasculature mediates normal development and physiology, as well as disease, when pathologically induced vessels are morphologically and functionally altered owing to an imbalance of angiogenesis-stimulating and angiogenesis-inhibiting factors. This review offers an overview of the angiogenic process and discusses recent findings that provide additional interesting nuances to this process, including the roles of intussusception and angiovasculogenesis, which may hold promise for future therapeutic interventions. In addition, we review the methodology, including those of in vitro and in vivo assays, which has helped build the vast amount of knowledge on angiogenesis available today and identify important remaining knowledge gaps that should be bridged through future research.

Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy, the standard of care for metastatic hormone receptor-positive (HR +)/human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC), has profoundly affected many cell types, including tumor cells, Tregs, cytotoxic T cells, and stem and progenitor cells. Therefore, it is reasonable to assume that the pretreatment status of tumor immunity may have predictive value in CDK4/6i efficacy.

A total of 404 patients were included in the analysis. The scores of the panimmune-inflammatory values (PIV) and PILE (PIV-LDH-ECOG), a candidate PIV-based scoring system, were calculated within one week before the initiation of CDK4/6i plus endocrine therapy (ET).

The median overall survival (OS) was 69.0 months (95% CI 51.1-86.8). The low-PIV subgroup had significantly longer progression-free survival (PFS) [23.9 vs. 18.8 months; HR = 1.817, 95% CI = 1.113-2.965, p = 0.017] and OS [73.6 vs. 37.7 months; HR = 2.338, 95% CI = 1.122-4.871, p = 0.023] than the high-PIV subgroup. In the low-risk PILE subgroup, PFS [37.0 vs. 15.8 months; HR = 2.751, 95% CI = 1.736-4.361, p < 0.001] and OS [73.6 vs. 35.1 months; HR = 3.854, 95% CI = 1.855-8.005, p < 0.001] were greater than in the high-risk PILE subgroup. The low-risk PILE subgroup was associated with a significantly better disease control rate (DCR) than the high-risk PILE subgroup (87.2% and 75.0%, p = 0.004). In the analysis of 112 patients treated with ET in the metastatic stage before CDK4/6i as a control group, PIV and PILE were not independent prognostic indicators.

Our study demonstrated that PIV and PILE scores could be predictive biomarkers for the treatment efficacy of CDK4/6is.

Oligo-metastatic urothelial carcinoma (OMUC), characterized by a limited number of metastases, demonstrates better survival outcomes compared to poly-metastatic urothelial carcinoma (PMUC), but some patients with OMUC exhibit poor prognosis. However, a comprehensive analysis of prognostic factors in OMUC remains lacking. This study aimed to determine prognostic factors in patients with OMUC from a multicenter dataset and evaluate the effect of existing predictive models.

This retrospective study included 443 patients with metastatic urothelial carcinoma (MUC) from 15 institutions (YUSHIMA study). OMUC involved cases with three or fewer metastases. Clinical data were analyzed for associations with overall survival (OS) utilizing Cox regression models. The effect of existing predictive models (Bajorin, Bellmunt, and Apolo) on OMUC prognosis was evaluated.

Patients with OMUC (n = 182) demonstrated better Eastern Cooperative Oncology Group-performance status (ECOG-PS) and lower visceral metastasis frequency compared to PMUC (n = 261). Patients with OMUC exhibited a median OS of 26.1 months vs. 13.7 months for PMUC (p < 0.01). Poor ECOG-PS, liver metastasis, and hypoalbuminemia appeared as independent poor prognostic factors for OS in OMUC. The Bajorin, Bellmunt, and Apolo models significantly correlated with OS in patients with OMUC (p < 0.01, for all).

Known prognostic factors for MUC were confirmed as significant prognostic factors for OS in OMUC, and existing prognostic models applied to OMUC. These results are expected to contribute to developing more effective treatment strategies for OMUC.

In a phytochemical investigation of the Tibetan medicine Marmoritis complanata (Dunn) A. L. Budantzev, 30 compounds were identified: 9 undescribed abietane diterpenoids (1-9), 7 undescribed isopimarane diterpenoids (12-18) and 14 known compounds (10, 11 and 19-30). The structures of the undescribed compounds were determined using one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, electronic circular dichroism and single-crystal X-ray diffraction. The concentration-gradient anti-inflammatory activity evaluation results indicated that most of the tested compounds exhibited concentration-dependent anti-inflammatory activity in the CuSO4-induced zebrafish model. Abietane (7, 9 and 10) and isopimarane diterpenoids (13, 15, 18 and 24) particularly showed the most significant anti-inflammatory activity, almost equal to that of a positive control. This study provides a basis for the development of anti-inflammatory drug lead compounds.

Castration-resistant prostate cancer (CRPC) presents a significant challenge due to its resistance to conventional androgen deprivation therapies. Urolithins, bioactive metabolites derived from ellagitannins, have recently emerged as promising therapeutic agents for CRPC. Urolithins not only inhibit androgen receptor (AR) signaling, a crucial factor in the progression of CRPC, but also play a key role in regulating oxidative stress by their antioxidant properties, thereby inhibiting increased reactive oxygen species, a common feature of the aggressive nature of CRPC. Research has shown that urolithins induce apoptosis and diminish pro-survival signaling, leading to tumor inhibition. This review delves into the intricate mechanisms through which urolithins exert their therapeutic effects, focusing on both AR-dependent and AR-independent pathways. It also explores the exciting potential of combining urolithins with androgen ablation therapy, opening new avenues for CRPC treatment.

In recent years, the continuous optimization of anti-tumor therapy has greatly improved the cancer-specific survival rate for patients with breast cancer (BC). The prevention and treatment of breast cancer-related heart diseases have become a new breakthrough in improving the long-term survival for BC patient. The cardiac damages caused by BC treatment are increasingly prominent among BC patients, of which ischemic heart disease (IHD) is the most prominent. Besides, the systemic inflammatory response activated by tumor microenvironment c an induce and exacerbate IHD and increase the risk of myocardial infarction (MI). Conversely, IHD can also exert detrimental effects on tumors. MI not only increases the risk of BC, but also induces specialized immune cell to BC and accelerates the progression of BC. Meanwhile, the treatment of IHD can also promote BC metastasis and transition to more aggressive phenotypes. Although BC and IHD are diseases of two independent systems, their crosstalk increases the difficulty of anti-cancer treatment and IHD management, which reduces the survival for both diseases. Therefore, this review mainly explores the mutual influence and underlying mechanisms between BC and IHD, aiming to provide insights for improving the long-term survival for patients with BC or IHD.

NLR family pyrin domain containing 3 (NLRP3) involves in inflammasome complex assembly and innate immunity. Activation of the NLRP3 inflammasome induces conformational alterations in protein complexes, influencing their interactions with other molecules, which in turn affects protein thermal stability. To investigate the proteome-wide thermal stability alterations induced by NLRP3 inflammasome activation, we conducted a comprehensive analysis of meltome dynamics using thermal proteome profiling (TPP). Our analysis identified 337 proteins exhibiting alterations in thermal stability upon NLRP3 inflammasome activation. Subsequently, we validated three proteins by the cellular thermal shift assay (CETSA). Notably, our findings reveal that the majority of these proteins tend to cluster into distinct macromolecular complexes. Furthermore, we identify FAM120A as a novel NLRP3 binding partner, with its suppression enhancing caspase-1 activation and IL-1β release in response to NLRP3 agonist. Collectively, these data provide a comprehensive framework for understanding the mechanisms of NLRP3 inflammasome activation and underscore the utility of TPP in exploring proteome-wide thermal stability changes during signaling transduction.

Gastric cancer is a major global health concern, often diagnosed at advanced stages, leading to poor prognosis. Proximal and distal gastric cancers exhibit distinct clinicopathological features.

To investigate the diagnostic value of hematological and inflammatory markers in differentiating proximal and distal gastric cancers and to evaluate their association with clinical outcomes.

A retrospective cohort study was conducted on 150 patients diagnosed with gastric adenocarcinoma through histopathological analysis. Patients were categorized into proximal gastric cancer and distal gastric cancer groups. Laboratory parameters were analyzed.

Of the 150 patients, 84 had proximal gastric cancer and 66 had distal gastric cancer. Dysphagia was significantly more common in the proximal gastric cancer group, while anemia and higher platelet-to-lymphocyte ratio values were observed in the distal gastric cancer group (P = 0.031). Tumor stage and neutrophil-to-lymphocyte ratio emerged as independent predictors of all-cause mortality. No significant differences were found in other laboratory or biochemical parameters between the groups.

Proximal and distal gastric cancers demonstrate distinct clinical and laboratory profiles. The platelet-to-lymphocyte ratio may serve as a valuable marker in differentiating cancer localization, while the neutrophil-to-lymphocyte ratio is a prognostic indicator for mortality. These findings highlight the potential of hematological markers in optimizing diagnosis and treatment strategies for gastric cancer.

The tumor stroma consists mainly of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions are altered during malignancy: tumor cells transform fibroblasts into cancer-associated fibroblasts, which exhibit immunosuppressive activities on which growth and metastasis depend. These include exclusion of immune cells from the tumor nest, cancer progression, and inhibition of T-cell-based immunotherapy. To understand these complex interactions, we measure the density of different cell types in the stroma using immunohistochemistry techniques on tumor samples from lung cancer patients. We incorporate these data into a minimal dynamical system, explore the variety of outcomes, and finally establish a spatio-temporal model that explains the cell distribution. We reproduce that cancer-associated fibroblasts act as a barrier to tumor expansion, but also reduce the efficiency of the immune response. Our conclusion is that the final outcome depends on the parameter values for each patient and leads to either tumor invasion, persistence, or eradication as a result of the interplay between cancer cell growth, T-cell cytotoxicity, and fibroblast activity. However, despite the existence of a wide range of scenarios, distinct trajectories, and patterns allow quantitative predictions that may help in the selection of new therapies and personalized protocols.

The impact of anastomotic leak (AL) on the long-term survival of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study investigated whether AL influences the long-term survival of patients with ESCC following McKeown esophagectomy.

An original database was queried to identify patients with ESCC who underwent McKeown esophagectomy between 2012 and 2020 at a high-volume cancer center. Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier (KM) curves. Cox regression analysis was used for multivariate analysis. Propensity score matching (PSM) was used to adjust for the confounding factors.

A total of 1614 patients were included, of whom 16.9% developed AL. In patients without neoadjuvant therapy, for patients with and without AL, the 5-year OS was 55.8% and 62.0%, and the 5-year DFS was 48.7% and 59.1%, respectively (OS: p = 0.37, DFS: p = 0.046). In the neoadjuvant cohort, for patients with and without AL, the 5-year OS was 57.9% and 63.2%, and the 5-year DFS was 55.4% and 58.8%, respectively (OS: p = 0.48, DFS: p = 0.78). Moreover, AL significantly increased the risk of distant recurrence in patients without neoadjuvant therapy (p = 0.023).

These findings suggest that AL negatively influences DFS in patients without neoadjuvant therapy, but does not significantly affect long-term survival in patients receiving neoadjuvant treatment. Intensive treatment and follow-up plan should be considered when patients without neoadjuvant therapy.

C-reactive protein (CRP) kinetics has emerged as a potential biomarker for predicting treatment response and survival in various tumors treated with immune checkpoint inhibitors (ICIs). However, data on CRP kinetics in melanoma are limited. This study evaluates the relationship between CRP kinetic groups and progression-free survival (PFS) and overall survival (OS) in 104 advanced melanoma patients treated with ICIs from 2015 to 2023. Patients were classified into four CRP kinetic groups: CRP flare responders, defined as patients whose CRP at least doubles within 1 month and then falls below baseline by 3 months; CRP responders, whose CRP decreases by ≥30% from baseline within 3 months without doubling; all-normal CRP, whose CRP remains below the upper limit of normal throughout the first 3 months; and CRP nonresponders, who do not meet these criteria. Amongst patients, 64.4% received anti-programmed death-1 monotherapy and 35.6% received the nivolumab-ipilimumab combination. Median PFS was 4.80 months in CRP nonresponders, 10.90 months in CRP responders, 8.83 months in CRP flare responders and 33.57 months in all-normal CRP patients (P < 0.001). Similarly, median OS was 11.9 months in CRP nonresponders, 38.1 months in CRP responders, 21.5 months in CRP flare responders and 54.5 months in all-normal CRP patients (P < 0.001). Multivariate analysis confirmed CRP kinetic groups as an independent predictor of PFS, OS and objective response. CRP kinetic classification is a simple prognostic tool for advanced melanoma patients treated with ICIs and is associated with improved survival outcomes, underscoring the clinical value of CRP monitoring.

Pathologies caused by parasitic infections, including protozoans and helminths remain a burden for healthcare in many countries. The DNA damage is produced by numerous parasites, both protozoans and helminths. However, the exact number of cancer-causing parasites and their role in neoplasma formation is still undetermined. The progression and dynamics of parasitic infections are significantly influenced by endogenously induced increase in oxidative stress (OS). Increased ROS production undermines antioxidant defense mechanisms by disrupting the balance between prooxidants and antioxidants, causing structural damage to important biomolecules, including host DNA. The generation of DNA damage possibly leads to the progression of carcinogenesis. However, direct DNA damage by parasites, eggs and factors released by parasites is also possible, and it leads to genomic instability that is a hallmark of most human and animal cancers. Understanding the way parasites induce DNA damage in the hosts may be helpful in the control of parasitic infections and the prevention of parasite-induced malignancies, ultimately benefiting the health of humans and animals. This review article offers an updated overview of parasitic infection-induced DNA damage mechanisms.

This systematic review and network meta-analysis (NMA) was to investigate the effects of different exercise modalities on inflammatory markers in cancer patients. Using the standardized mean difference (SMD) as the effect size, a Bayesian random-effects network meta-analysis and regression analysis were conducted. Searches were performed across five databases for randomized controlled trials (RCTs) involving cancer patients, with exercise as the intervention, reported outcomes related to inflammatory markers, and interventions lasting more than four weeks, up to June 2024. A total of 57 RCTs (3106 patients) were included. The Cochrane risk of Bias Tool was utilized to assess the RCTs, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was employed to evaluate the quality of evidence. NMA results indicate that regular exercise is effective in reducing inflammation in cancer patients, with combined high-intensity aerobic and resistance exercises proving to be the most beneficial. The type, intensity, and total volume of exercise are critical factors in achieving positive outcomes. It is recommended to design exercise programs for cancer patients that combine aerobic and resistance training, with a gradual increase in intensity to ensure safety.

Chronic inflammation remains a major global health concern, necessitating the development of advanced tools for continuous, precise monitoring. This study introduces a novel, clinically impactful triple-mode probe that integrates colorimetric, fluorescence, and surface-enhanced Raman scattering (SERS) signals, offering unparalleled multimodal detection capabilities. The probe's design leverages europium chelate-doped polystyrene nanoparticles (ECNPs), ensuring minimal signal cross-interference through a long Stokes shift. A key innovation is the development of a multimodal mapping algorithm that seamlessly integrates these optical signals, providing a sensitive and robust platform for biomarker detection with broad dynamic ranges. The probe's clinical relevance is demonstrated by its application in lateral flow assays (LFAs) for detecting C-reactive protein (CRP) levels, achieving a detection limit of 6.31 ng/mL and dynamic ranges from 23.13 to 2000 ng/mL, significantly outperforming single-mode detection methods. In clinical validation using urine samples from 31 patients, the triple-mode LFA showed excellent correlation (0.9377) and agreement (93.55 %) with gold standard enzyme-linked immunosorbent assay (ELISA) results. This demonstrates that the proposed multimodal platform offers a highly sensitive, cost-effective, and versatile tool for monitoring inflammation and other disease biomarkers, with substantial potential for clinical applications in diagnostics and disease management.

CXCL2 (C-X-C Motif Chemokine Ligand 2), a constituent of the C-X-C chemokine subfamily, serves as a powerful chemotactic factor for neutrophils, facilitating leukocyte recruitment and movement while initiating an inflammatory response. Recent investigations have demonstrated the pivotal involvement of CXCL2 in carcinogenesis. Within the tumor microenvironment, CXCL2 modulates cellular activity primarily via its interaction with the CXCR2 receptor. The activation of signaling pathways, including ERK/MAPK, NF-κB/MAPK, PI3K/AKT, and JAK/STAT3, highlights CXCL2's inclination to promote tumorigenesis. Furthermore, the role of CXCL2 encompasses inflammatory conditions like lung inflammation, atherosclerosis, and obesity. This article examines the structural characteristics, biological roles, and molecular foundation of CXCL2 in carcinogenesis and inflammatory disorders.

A diet rich in fruits, vegetables, coffee, and tea, limited red meat, and moderate alcohol intake may reduce the risk of renal cell carcinoma (RCC). The anti-inflammatory potential of diet has been proposed as a mechanism influencing cancer risk. This study assessed the association between an anti-inflammatory diet and RCC risk.

Data from two Swedish cohorts, the Swedish-Mammography-Cohort and the Cohort-of-Swedish-Men, were analysed. Dietary habits were assessed using a 96-item food frequency questionnaire. The Anti-Inflammatory Diet Index (AIDI), composed of 16 food groups (11 anti-inflammatory and 5 pro-inflammatory), was used to score dietary patterns. RCC cases were identified from the Swedish Cancer Register using ICD-10 codes, and Cox proportional hazards models were used to estimate hazard ratios based on AIDI quartiles.

Among 71,421 participants, 431 RCC cases were identified during a 19.7-year follow-up. Higher AIDI scores were associated with a lower RCC risk (HR for Q4 vs. Q1: 0.68, CI: 0.52-0.89). In sex-stratified analyses (p-for heterogeneity = 0.006), the association was stronger in among women (HR: 0.47, CI: 0.30-0.75) but less clear in among men (HR: 0.83, CI: 0.63-1.24).

These data suggest that adherence to an anti-inflammatory diet may confer a reduced risk for RCC, especially among women.

Trials have shown promising clinical activity of the selective SYK inhibitor entospletinib in patients with high expressing HOXA9/MEIS1 acute leukemias. As the development of resistance mechanisms is a common problem in the use of targeted drugs, we performed a chemical library screen to identify drug sensitivities in SYK inhibitor resistant AML cells. We identified that SYK inhibitor resistant cells displayed an increased sensitivity to glucocorticoids. Glucocorticoids are potent immunosuppressants which work in part by inhibiting the transcription of cytokine genes. RNA sequencing of entospletinib resistant cells revealed a strong enrichment of inflammatory response and TNFα signaling via NF-κB gene sets in comparison to naive cells. Naive AML cells treated with entospletinib showed a strong downregulation of the same gene sets which were upregulated in the resistant state. Our data suggest that inflammatory signaling pathways play a role in entospletinib resistant AML cells.

The prognostic significance of the C-reactive protein-albumin-lymphocyte (CALLY) index in digestive system neoplasms (DSNs) has been investigated in several studies, but inconsistencies remain between the results of different studies. Therefore, the aim of this study was to confirm the prognostic significance of CALLY in patients with DSNs and its association with clinicopathological characteristics (CPCs).

The databases PubMed, Cochrane Library, Web of Science, Research Square and Embase were systematically searched for clinical trials with databases up to 1 November 2024. The value of CALLY in predicting overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) versus cancer-specific survival (CSS) in patients with DSNs was confirmed by calculating the combined hazard ratio (HR) and 95% CI. The combined OR and 95% CI were calculated to assess the association between CALLY and CPCs in patients with DSNs.

A total of 18 studies with 7916 patients with DSNs were included in this study. Pooled analysis showed that lower CALLY was associated with poor OS, DFS, RFS and CSS were significantly associated. In addition, low CALLY index was associated with male gender, T3-T4, lymph node metastasis, lymph vessel invasion, complications, stage III-IV and surgical approach were significantly associated. However, there was no association between low CALLY index and histological type, adjuvant chemotherapy, and neoadjuvant chemotherapy.

In this meta-analysis, a low CALLY index was significantly associated with poor OS, DFS, RFS and CSS in patients with DSNs and with several CPCs in patients with DSNs.

PROSPERO CRD42024622973.

Viewing the hallmarks as a sequence of adaptations captures the "why" behind the "how" of the molecular changes driving cancer. This eco-evolutionary view distils the complexity of cancer progression into logical steps, providing a framework for understanding all existing and emerging hallmarks of cancer and developing therapeutic interventions.

The ketogenic diet (KD) has attracted attention in recent years for its potential anticancer effects. KD is a dietary structure of high fat, moderate protein, and extremely low carbohydrate content. Originally introduced as a treatment for epilepsy, KD has been widely applied in weight loss programs and the management of metabolic diseases. Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells, thereby inhibiting tumor angiogenesis, reducing oxidative stress in normal cells, and affecting cancer cell signaling and other processes. Moreover, KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota, enhance the efficacy of standard cancer treatments, and mitigate the complications of chemotherapy. However, controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer. Therefore, this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.

Breast cancer (BC) is the leading cancer among women globally, which has the highest incidence and mortality rate in over a hundred countries. This study was intended to discover a new prognostic biomarker, facilitating personalized treatment approaches.

RNA sequencing data from The Cancer Genome Atlas database and Gene Expression Omnibus database were utilized to download to evaluate expression levels and prognostic significance of Keratin 14 (KRT14). Methylation of KRT14 was also assessed. The CIBERSORT and single-sample gene set enrichment analysis algorithms were applied to explore the connection between KRT14 and the tumor microenvironment. Primary drugs' sensitivity and potential small molecule therapeutic compounds were analyzed through the "pRRophetic" R package and the Connectivity Map. The prognostic value of KRT14 was additionally corroborated through a comparison of protein levels in peritumoral and cancerous tissues via immunohistochemistry. Moreover, an immune-related prognostic model based on KRT14 was designed to enhance the prediction accuracy for the prognosis of BC patients.

The study found that KRT14 expression was generally downregulated in BC, correlating strongly with poor prognosis. Compared to normal tissues, the methylation level of KRT14 was higher in BC tissues. Lower expression of KRT14 was linked to decreased anti-tumoral immune cells infiltration and increased immunosuppressive cells infiltration. Sensitivity to various key therapeutic drugs was lower in groups with diminished KRT14 expression. In addition, several potential anti-BC small molecule compounds were identified. The model designed in this study significantly enhanced the predictive capability for BC patients compared to predictions based solely on KRT14 expression levels.

Overall, KRT14 was closely correlated with the prognosis in BC, making it a reliable biomarker.

Epidemiologic research has linked periodontitis to several types of cancer, particularly breast cancer. Although clinical evidence indicates a higher risk of breast cancer in women with periodontitis than in those without, few studies have explored whether the risk of periodontitis is higher in women with breast cancer than in those without. In this study, we examined the incidence of periodontitis in patients with breast cancer and identified potential interventions for its prevention.

This retrospective cohort study included data from the National Health Insurance Research Database of Taiwan. We identified women who received a diagnosis of breast cancer between 2010 and 2019 and included a 1:1 matched control cohort with no breast cancer. Subsequently, we analyzed the risk of periodontitis by using Cox proportional-hazards models while adjusting for sociodemographic factors, comorbidities, and treatment regimens.

In 82,146 matched pairs, the breast cancer cohort was at a 51 % higher risk of periodontitis compared with the control cohort (adjusted hazard ratio = 1.51, 95 % confidence interval = 1.43-1.60). The stratified analysis revealed the same results. The risk of breast cancer was higher in younger patients than in older patients, whereas the risk of periodontitis was significantly lower in patients who underwent surgery, radiotherapy, chemotherapy, or hormone therapy compared with those who did not.

Breast cancer increases the risk of periodontitis, particularly in younger patients. These patients should receive regular dental care to prevent and manage periodontitis. Anticancer treatments may mitigate the risk of periodontitis in patients with breast cancer.

This study aimed to evaluate the potential of ethanolic extract of propolis on the secondary lesions of the liver, renal, and pancreatic that were derived by primary colorectal cancer, and comparison of the ethanolic extract of propolis with the vitamin E. The groups included the control, ethanolic extract of propolis, vitamin E, dimethylhydrazine, dimethylhydrazine + ethanolic extract of propolis, and dimethylhydrazine + vitamin E. After 13 weeks of treatment, the blood and tissue samples were taken from all the rats, and alanine transaminase, aspartate transaminase, alkaline phosphatase, uric acid, creatinine, blood urea nitrogen, insulin, amylase, and lipase indices along with the tissue pathological examination of the kidney, liver, and pancreas were evaluated. Ethanolic extract of propolis effectively alleviated the colorectal cancer-induced secondary lesions in the liver by significantly lowering the alanine transaminase significantly. Ethanolic extract of propolis significantly decreased uric acid in rats; and also significantly elevated the pancreatic insulin. In addition, inflammation and cell necrosis indices in all these tissues were significantly reduced when ethanolic extract of propolis was consumed compared to the dimethylhydrazine group. It seemed ethanolic extract of propolis showed high antioxidant, anticancer, and anti-inflammatory potentials, and can be used practically to reduce the side lesions of colorectal cancer.

A systemic analysis was performed to evaluate the prognostic utility of the Glasgow prognostic score (GPS) and the modified (m)GPS in cancer patients treated with immune checkpoint inhibitors (ICI). The PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for entries added until May 1st, 2023, to obtain relevant articles for this study. The analysis examined several clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate and disease control rate (DCR). In this analysis, a total of 38 articles with 3,772 patients were included. The pooled results indicated that patients with high GPS levels had shorter OS [GPS 2 vs. 0, hazard ratio (HR): 4.35, P<0.001; GPS 1 vs. 0, HR: 2.00, P<0.001; GPS 2 vs. 1/0, HR: 2.62, P<0.001; GPS 2/1 vs. 0, HR: 2.60, P<0.001) and PFS (GPS 2 vs. 0, HR: 2.11, P=0.001; GPS 1 vs. 0, HR: 1.33, P=0.001; GPS 2 vs. 1/0, HR: 2.11, P<0.001; GPS 2/1 vs. 0, HR: 1.62, P<0.001], as well as a lower DCR [GPS 2 vs. 1/0, odds ratio (OR): 0.53, P<0.001, GPS 2/1 vs. 0, OR: 0.51, P<0.001]. It was also found that patients with high mGPS levels had poorer OS (mGPS 2 vs. 0, HR: 3.15, P<0.001; mGPS 1 vs. 0, HR: 1.70, P<0.001; mGPS 2 vs. 1/0, HR: 1.95, P=0.049; mGPS 2/1 vs. 0, HR: 3.14, P=0.041; continuous variables, HR: 1.52, P<0.001) and PFS (mGPS 2 vs. 0, HR: 2.70, P<0.001; mGPS 1 vs. 0, HR: 1.74, P=0.016; mGPS 2 vs. 1/0, HR: 1.91, P=0.044; continuous variables, HR: 1.29, P<0.001), and lower DCR (mGPS 2 vs. 1/0, HR: 0.46, P<0.001). In conclusion, the GPS and mGPS were reliable predictors of outcomes in cancer patients treated with ICIs.

Pancreatic cancer is an aggressive malignancy characterized by rapid progression, unfavorable outcomes, and a low early detection rate. Elucidating the mechanisms underlying the onset and progression of pancreatic tumors is essential for early detection and for developing preventive measures. Even though human rhomboid family-1 (RHBDF) acts as an oncogene in various tumors, the role of RHBDF in pancreatic cancer progression remains unexplored. Here, publicly available datasets, including samples of chronic pancreatitis associated with pancreatic cancer from our center, were used for bioinformatics analyses, including differential expression, survival, and enrichment studies. The findings were validated by immunohistochemical staining and in vitro experiments. We found that RHBDF1 was significantly upregulated in tumor samples relative to adjacent non-tumor and pancreatitis tissues, and its expression increased in correlation with the progression of pancreatitis to cancer. Furthermore, RHBDF1 promoted the proliferation, migration, and invasion of pancreatic cancer cells, and in vivo studies demonstrated that RHBDF1 promoted pancreatic cancer progression, tissue fibrosis, and the formation of new blood vessels. RNA-sequencing and cell functional experiments indicated that RHBDF1 promotes the progression of pancreatic cancer through the SRC-YAP signaling pathway. In summary, the pancreatitis-cancer transformation-related factor, RHBDF1, promotes pancreatic cancer progression by activating the SRC-YAP signaling cascade, indicating that RHBDF1 could be a viable target for the diagnosis and treatment of early-stage pancreatic cancer.

Chronic inflammation is a common hallmark of many chronic diseases. Although exercise holds paramount importance in preventing and managing chronic diseases, adherence to exercise programs can be challenging for some patients. Consequently, there is a pressing need to explore alternative strategies to emulate the anti-inflammatory effects of exercise for chronic diseases.

This review explores the emerging role of green tea bioactive components as potential mitigators of chronic inflammation, offering insights into their capacity to mimic the beneficial effects of exercise. We propose that bioactive components in green tea are promising agents for suppressing chronic inflammation, suggesting their unique capability to replicate the health benefits of exercise.

This review focuses on several key concepts, including chronic inflammation and its role in chronic diseases, the anti-inflammatory effects of regular exercise, and bioactive components in green tea responsible for its health benefits. It elaborates on scientific evidence supporting the anti-inflammatory properties of green tea bioactive components, such as epigallocatechin gallate (EGCG), and theorizes how these bioactive components might replicate the effects of exercise at a molecular level. Through a comprehensive analysis of current research, this review proposes a novel perspective on the application of green tea as a potential intervention strategy to suppress chronic inflammation, thereby extending the benefits akin to those achieved through exercise.

Epithelial ovarian cancer (EOC) is a gynecological tumor with high mortality. Despite aggressive treatment, survival rates for patients with advanced EOC are low, and more effective methods of diagnosis and treatment are urgently needed. Inflammation and cancer are strongly associated; however, the mechanisms that mediate this relationship are not fully understood. In this study, we found that the expression of interleukin-1β (IL-1β), a proinflammatory cytokine, increased in an ovarian cancer tissue microarray (TMA) and inhibited A2780 and SKOV3 cell viability and metastasis. Recombinant IL-1β protein and the overexpression of IL-1β decreased the proliferation and metastasis of ovarian cancer cells. IL-1β deficiency promoted proliferation and metastasis. Moreover, transcriptome sequencing revealed that IL-1β downregulates the expression of matrix metalloproteinase 12 (MMP12). The signaling pathway involving MAPK/AP-1/MMP12 is involved in IL-1β-regulated ovarian cancer progression. Overall, we found that the proinflammatory cytokine IL-1β inhibits ovarian cancer cell viability and metastasis. These findings provided deeper insights into inflammation and cancer progression.

Mycobacterium tuberculosis (Mtb) causes 1.25 million deaths a year. However, tuberculosis (TB) pathogenesis remains poorly understood and is not fully recapitulated in standard mouse models. Here we find that gene signatures from three different Mtb-susceptible mouse models predict active TB disease in humans significantly better than a signature from resistant C57BL/6 (B6) mice. Conserved among susceptible mice, non-human primates, and humans, but largely absent from B6 mice, was Mtb-induced differentiation of macrophages into an Spp1 + differentiation state. Spp1 + macrophages expressed high levels of immunosuppressive molecules including IL-1 receptor antagonist (IL-1Ra). IL-1Ra was previously reported to cause Mtb susceptibility in one mouse model, but whether IL-1Ra is broadly important remains uncertain. Here we report that enhancement of IL-1 signaling via deletion of IL-Ra promoted bacterial control across three susceptible mouse models. We found IL-1 signaling amplified production of multiple cytokines by lymphoid and stromal cells, providing a multifactorial mechanism for how IL-1 promotes Mtb control. Our results indicate that myeloid cell expression of immunosuppressive molecules, in particular IL-1 receptor antagonist, is a conserved early mechanism limiting Mtb control in mice, non-human primates, and humans.

It has been suggested that long-term risk for incident cancer is increased in patients operated with cardiopulmonary bypass. We compared the risk for incident cancer and cancer-specific death between patients undergoing coronary artery bypass grafting (CABG) with and without cardiopulmonary bypass.

All patients without a history of cancer undergoing first-time CABG in Sweden during 1997-2020 were included in a nationwide population-based observational cohort study. Individual patient data from the SWEDEHEART registry and 4 other mandatory national registries were merged. The incidence of new cancer was compared between patients operated with or without cardiopulmonary bypass using multivariable Cox proportional hazards regression models adjusted for baseline characteristics, co-morbidities, socioeconomic factors and time of surgery. A propensity score-matched analysis with 3735 well-balanced pairs was also performed.

A total of 81 097 patients undergoing CABG with (n = 77 345) and without cardiopulmonary bypass (n = 3752) were included. Median follow-up was 8.2 (interquartile range 4.0-13.2) years. The crude event rates were 2.71 and 2.68 per 100 person-years in the patients operated with and without cardiopulmonary bypass, respectively. There was no difference in the adjusted risk for cancer between the groups [adjusted hazard ratio 0.95 (95% confidence interval; CI 0.90-1.01)] or in the risk for cancer-specific death between the groups [adjusted hazard ratio 0.99 (95% CI 0.89-1.09)]. The propensity score-matched analysis showed similar results [hazard ratio 0.96 (95% CI 0.89-1.04) and 0.99 (95% CI 0.85-1.13)], respectively.

Cardiopulmonary bypass is not associated with an increased risk of incident cancer or cancer-specific mortality in patients undergoing CABG.

Chronic inflammation is a well-established risk factor for cancer, but the underlying molecular mechanisms remain unclear. Using a mouse model of colitis, we demonstrate that colonic stem cells retain an epigenetic memory of inflammation following disease resolution, characterized by a cumulative gain of activator protein 1 (AP-1) transcription factor activity. Further, we develop SHARE-TRACE, a method that enables simultaneous profiling of gene expression, chromatin accessibility and clonal history in single cells, enabling high resolution tracking of epigenomic memory. This reveals that inflammatory memory is propagated cell-intrinsically and inherited through stem cell lineages, with certain clones demonstrating dramatically stronger memory than others. Finally, we show that colitis primes stem cells for amplified expression of regenerative gene programs following oncogenic mutation that accelerate tumor growth. This includes a subpopulation of tumors that have exceptionally high AP-1 activity and the additional upregulation of pro-oncogenic programs. Together, our findings provide a mechanistic link between chronic inflammation and malignancy, revealing how long-lived epigenetic alterations in regenerative tissues may contribute to disease susceptibility and suggesting potential therapeutic strategies to mitigate cancer risk in patients with chronic inflammatory conditions.

Multiple myeloma has become the second most common hematologic malignancy threatening human health with the increasing incidence in the population, and the emergence of drug resistance in its treatment has become a problem that needs to be solved urgently. Recent studies have shown that the immune system is closely related to the development of multiple myeloma, and immune senescence plays an extremely critical role in MM treatment resistance. In this paper, we review the connection between immune senescence and the development of MM and its possible role in the drug resistance of MM treatment, to provide new research ideas for the in-depth study of the mechanism of immune senescence and the search for new immunotherapeutic targets to overcome the phenomenon of drug resistance in the immunotherapy of MM patients.

Background/Objectives: To evaluate the prognostic value of easily obtainable biomarkers for patients undergoing percutaneous microwave ablation (MWA) for colorectal liver metastases (CLMs). Prior studies showed that simple biomarkers, such as the lymphocyte-to-monocyte ratio (LMR), albumin-to-globulin ratio (AGR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), as well as cancer-specific markers, like carcinoembryonic antigen (CEA), might have a prognostic role in various malignancies; however, none of these were assessed in patients undergoing MWA for CLMs. Methods: Based on the simple laboratory results, which were determined prior to the ablation, several biomarkers, including the LMR, AGR, PLR, and NLR, were calculated. The log-rank test's optimal cutoff points for continuous variables were determined. Subsequently, univariable and multivariable Cox regression models were utilized to determine the association between various features and overall survival (OS). Results: This study included 57 CLM patients with a mean age of 63 ± 12.5 years at the time of ablation with a mean follow up of 30.9 months. The univariable model demonstrated that a high level of CEA (cutoff: 29.1 ng/mL; HR: 3.70) and a high LMR (cutoff: 5.32; HR: 4.05) were related to worse OS, whereas a high NLR (cutoff: 2.05; HR: 0.31) and primary left-sided colon cancer (HR: 0.36) were positive prognostic factors. The multivariable regression model confirmed these findings, with the exception of the LMR, which was no longer significantly associated with OS. Conclusions: This study demonstrates the feasibility of overall survival prediction and thus patient stratification based on easily obtainable biomarkers and clinicopathological features in CLM patients undergoing MWA.

Programmed necrosis, a controlled cell death method that bypasses resistance mechanisms that render apoptosis ineffective, is a potential cancer treatment target. Due to their diverse biological activities and low side effects, natural products are being explored as modulators of programmed necrosis pathways. This review highlights the potential of natural compounds to target cancer cells while preserving healthy tissues and their interaction with essential programmed necrosis mechanisms like ferroptosis and necroptosis. Recent developments have identified various types of programmable necrosis, including necroptosis, ferroptosis, pyroptosis, proptosis, mitochondrial permeability transition-driven necrosis, and oncosis. Natural compounds are increasingly being utilized as a primary source of anti-cancer medications, providing new cancer treatments. This review demonstrates the molecular mechanisms behind lipid peroxidation, mixed lineage kinase domain-like protein, and receptor-interacting protein kinases (RIPK1 and RIPK3) inducing cell death. Recent research has identified natural compounds like polyphenols, alkaloids, and terpenoids that can modulate pathways and benefit preclinical cancer models. The review underscores the potential of natural compounds in developing innovative cancer treatments by integrating pharmacology and cellular signaling knowledge. Integrating natural compound studies and programmed necrosis research presents a promising avenue for oncologists to overcome treatment resistance. Natural compounds have shown potential in developing programmed necrosis as a novel cancer treatment approach, enhancing therapeutic effectiveness and minimizing side effects through preclinical research, pharmacology, and molecular biology.

The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.