Ovarian cancer was the eighth most frequently diagnosed cancer among women in 2022. The global age-standardized incidence rate of ovarian cancer decreased from 7.22/100,000 to 6.71/100,000 from 1990 to 2021. However, incidence trends varied across countries. Declining ovarian cancer incidence rates were reported in high-income countries, such as the United States, Austria, the Netherlands, and Norway, while there were increasing incidence rates in Africa and parts of Asia, including Japan and India. The global age-standardized mortality rate of ovarian cancer decreased from 4.73/100,000 to 4.06/100,000 between 1999 and 2021 with varying trends among countries. Moreover, the age-standardized 5-year net ovarian cancer survival rate in most countries remained < 50%. Several specific factors related to ovarian cancer risk have been identified, including reproductive factors, use of oral contraceptives, anti-inflammatory diets, endometriosis, pelvic inflammatory disease, obesity, diabetes, and occupational asbestos exposure. No screening or prevention strategy has been proven effective in downstaging or reducing mortality from ovarian cancer in an average-risk population without a family cancer history or pathogenic variants. Indeed, risk-reducing salpingo-oophorectomy remains the gold standard for lowering the risk of ovarian cancer in high-risk individuals with hereditary mutations. This review provides a comprehensive overview of the epidemiology, risk factors, screening, and prevention of ovarian cancer, aiming to offer a global perspective on public health strategies for addressing the disease.
OBJECTIVE:Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. This study was aimed at estimating regional and national variations in lifetime CRC risk worldwide. METHODS:CRC data were extracted from GLOBOCAN 2022, including 185 countries, and population and all-cause mortality data were sourced from the United Nations. The world was divided into 20 geographical regions and categorized by Human Development Index (HDI). Lifetime CRC risk was estimated with the life table method, adjusted for multiple primary cancers. RESULTS:In 2022, the lifetime risks of developing and dying from CRC were 2.69% [95% confidence interval (CI): 2.68-2.70] and 1.39% (95% CI: 1.39-1.40), respectively. Men had a higher risk of colon cancer than rectal cancer, and higher CRC risk than women. Lifetime risk varied by region and HDI: regions with very high, high, moderate, and low HDI had incidence risks of 5.17%, 2.75%, 0.72%, and 0.57%, respectively, and mortality risks of 2.48%, 1.50%, 0.44%, and 0.41%, respectively. Australia/New Zealand had the highest incidence risk (7.41%, 95% CI: 7.30-7.52), and Northern Europe the highest mortality risk (3.28%, 95% CI: 3.24-3.32). Risks were stable before 40 years of age, peaked in middle age, and declined after 70 years of age. Temporally, Thailand had the highest increasing trend in lifetime risk, whereas the United States and Austria showed a decreasing trend. CONCLUSIONS:Lifetime CRC risk differs by subtype, sex, HDI, and geography, and residual risk gradually decreases with age. Targeted primary prevention strategies should be implemented in various countries and regions to mitigate CRC burden.
Human papillomavirus(HPV)is the most prevalent sexually transmitted infection worldwide1.More than 200 HPV geno-types have been identified and are classified as high-risk HPV(HR-HPV)or low-risk HPV(LR-HPV)according to their onco-genic potential.
OBJECTIVE:Breast cancer is the most frequently diagnosed cancer among women worldwide and is a leading cause of cancer-related deaths. Comparative assessments of breast cancer lifetime risks across populations are limited. This study estimated the global, regional, and national lifetime risks, temporal trends, and socioeconomic inequalities in the burden of breast cancer. METHODS:Using incidence and mortality data from GLOBOCAN 2022 (185 countries) and United Nations population and all-cause death data, lifetime risks were calculated using the adjusted for multiple primaries (AMP) method, which could adjust for multiple primary cancers, competing risks of other causes death, and life expectancy. Longitudinal data of breast cancer incidence from 2003-2017 were retrieved from the Cancer Incidence in Five Continents (CI5) Plus database. The temporal trends for breast cancer deaths were abstracted from the WHO Mortality Database. The lifetime risk of developing and dying from breast cancer were analyzed by socioeconomic characteristics, 20 predefined geographic regions and menopausal status. RESULTS:The overall worldwide lifetime risk of developing and dying from breast cancer was 5.51% (95% CI: 5.50%-5.52%) and 1.82% (95% CI: 1.82%-1.83%) in 2022, respectively. The estimated lifetime risks of developing breast cancer had a positive relationship with Human Development Index (HDI) levels and corresponding risks of 10.37%, 4.42%, 2.96%, and 2.91% in very high, high, middle, and low HDI regions, respectively. Very high HDI regions presented the highest lifetime risk of breast cancer death (2.70%), followed by low HDI (1.70%), medium HDI (1.54%), and high (1.38%) HDI regions. A significant correlation was identified between lifetime risks and health economics capacity. The lifetime risk of developing and dying from breast cancer primarily involved individuals ≥ 55 years of age with remaining risks of 3.77% (developing) and 1.43% (dying) from 55 years to death. The proportion of lifetime risks among individuals 0-44 years of age was higher in Africa regions compared to other regions. In surveillance data from 36 countries, a significant increasing trend in the average annual percentage change (AAPC) was noted in 32 countries, which ranged from 0.17% in the United States to 5.84% in the Republic of Korea. CONCLUSIONS:Globally, an estimated 1 in 18 individuals were diagnosed with breast cancer during their lifetime and approximately 1 in 55 died from the disease in 2022. Lifetime risk of breast cancer disparities reveal the socioeconomic inequalities of breast cancer. Therefore, country-tailored intervention plans for breast cancer require prioritization within precision prevention to mitigate global breast cancer inequities and burden.
Gastric cancer(GC)remains a leading cause of cancer mor-tality worldwide1.Helicobacter pylori(H.pylori)infection is the dominant etiologic factor2,yet GC also arises in indi-viduals without infection or after eradication,suggesting alternative carcinogenic pathways3.
The paradigm of cancer screening is poised for a transfor-mation from single-cancer,modality-specific tests toward a unified approach enabled by liquid biopsy.
The human gut microbiome plays critical roles in cancer.These gut microorganisms and their derivatives influence nearly every aspect of the disease,including tumor develop-ment and progression to metastasis,as well as therapeutic efficacy.Given this importance,emerging research is focusing on novel strategies aimed at targeting the gut microbiome to improve patient outcomes.This special issue brings together a collection of Reviews,Letter,and Research Articles exploring the multifaceted roles of the microbiome,providing functional and mechanistic insights,and discussing the clinical potential of current microbiome-targeting strategies.
The introduction of immune checkpoint inhibitors(ICIs)has substantially improved therapeutic outcomes in patients with non-small cell lung cancer(NSCLC)but marked inter-indi-vidual variability in treatment response persists1.Increasing evidence indicates that the gut microbiota has a critical role in regulating antitumor immune responses through the gut-organ axis,thereby influencing the efficacy and toxicity of systemic anticancer therapies2.Among microbiota-mod-ulating strategies,antibiotics and probiotics have attracted considerable interest.Nevertheless,the clinical impact of antibiotics and probiotics on treatment outcomes in NSCLC has not been comprehensively and systematically evaluated.Against this background,a meta-analysis was performed to determine the associations between antibiotic exposure or probiotic supplementation and clinical outcomes in patients with NSCLC,focusing on the objective response rate(ORR),progression-free survival(PFS),and overall survival(OS).
Objective: Left- and right-sided colorectal cancer (CRC) exhibit distinct molecular and clinicopathologic features. However, little is known about the spatial heterogeneity of microbial signatures. In this study the profiles and ecologic patterns of disease-associated intestinal microbiome were investigated in patients with an adenoma(s) or CRC at different anatomic locations. Methods: A total of 690 stool, colonic aspirate, and mucosal biopsy samples were prospectively collected from 32 healthy, 30 adenoma, and 31 CRC patients. Results: CRC was associated with alterations in fecal and mucosal microbiomes. Furthermore, the overall composition of the mucosal microbiome, stratified by metacommunities, differed between the patients with left- and right-sided neoplastic lesions. Patients with right-sided CRC had an elevated inter-phylum ecologic network, while patients with left-sided CRC had an enriched abundance of Fusobacterium . Interestingly, rectal neoplasia harbored a tumor microbiome that was distinctly different from the tumor microbiome at other anatomic sites. Conclusion: The mucosal microbiome of right-sided CRC was distinctly different from the mucosal microbiome of left-sided CRC patients, suggesting distinct microbial ecology and heterogeneous host-microbial ecologic relationships that may contribute to differences in the tumor microenvironment between left- and right-sided CRC.
Immunogenic cell death (ICD), a special form of cell death, transforms "cold" tumors into "hot" tumors by fulfilling the following three key conditions: antigenicity; adjuvanticity; and a suitable tumor microenvironment (TME). Tumor cells release damage-associated molecular patterns (DAMPs) during ICD, thereby activating the dendritic-cytotoxic T cell axis to elicit systemic antitumor immune responses. However, drug resistance and immune-related adverse effects often limit traditional ICD inducers, including chemotherapy and radiotherapy. Notably, microbiota and microbial metabolites can trigger ICD in tumor cells, leading to the release of DAMPs, modulation of immune cell functions, and TME remodeling. This study comprehensively reviews the mechanisms underlying ICD regulation via microbiota and microbial metabolites. In addition, this review examines emerging strategies, including engineered microbiota, microbial-based combination therapies (such as incorporating immune checkpoint inhibitors or chemotherapy), and dietary interventions. Despite challenges associated with individual microbiota variability and mechanistic complexity, this study highlights the potential of microbiota-mediated ICD modulation as a novel paradigm for personalized cancer therapy, thereby providing insights for future directions of scientific research.
OBJECTIVE:Dietary nitrate has been increasingly recognized as a potential carcinogen associated with gastritis. In this study the mechanistic role of a high-nitrate diet (NaD) in driving gastritis was elucidated with a focus on modulation of the gastric microbiota composition and metabolomic profiles. METHODS:Animals were randomly assigned to two dietary intervention groups using a C57BL/6 mouse model: a NaD containing 7.5% nitrate; or a standard normal diet (ND). Gastric microbiota composition was characterized based on full-length 16S rRNA sequencing and gastric metabolite profiles were analyzed using high-performance liquid chromatography-mass spectrometry (HPLC/MS). Finally, the roles of the microbiome and metabolites in gastritis development were validated using the human gastric epithelial cell line (GES-1), as well as conventional and germ-free mouse models. RESULTS:NaD induced gastritis in conventional mice compared to ND-fed mice. In addition, NaD incited the infiltration of macrophages and neutrophils with elevated levels of inflammatory cytokine genes (IL-17a, Ccl20, Cxcl5, IL-6, and Ccl2). A significant shift in the composition of the gastric microbiota occurred with an increase in pathogenic bacteria (Enterococcus gallinarum, Prevotella timonensis, and Mycobacterium gordona) and a decrease in probiotics (Roseburia hominis, Clostriduim scindens, and Faecalibacterium prausnitzii). Furthermore, NaD induced alterations in the metabolic profile, marked by an elevated level of 5-hydroxyindoleacetate (5-HIAA), a key downstream metabolite of the tryptophan metabolic pathway. Notably, 5-HIAA also upregulated the levels of inflammatory cytokines in the human gastric epithelial GES-1 cell line. In addition, both E. gallinarum colonization and 5-HIAA exposure significantly increased inflammatory responses in conventional and germ-free mouse models. CONCLUSIONS:NaD drives gastritis in mice by inducing gastric microbial dysbiosis and metabolomic dysregulation with elevated 5-HIAA.
Colorectal cancer (CRC) is among the most common malignant tumors and remains a leading cause of cancer-related mortality worldwide. The gut microbiota and metabolites, which are modulated by host genetics and environmental exposures, have emerged as key contributors to the pathogenesis of CRC. A key feature of gut dysbiosis in CRC is the enrichment of pathogenic bacteria alongside the depletion of beneficial commensals. Probiotic supplementation has been shown to counteract this imbalance and suppress tumor progression. Mechanistically, probiotics suppress CRC development through multifaceted actions, including directly inhibiting tumor cell growth, reducing inflammation, reinforcing the intestinal barrier, and reprogramming host immunity. This review summarizes evidence on the inhibitory role of probiotics in CRC, evaluates the potential of probiotics as predictive biomarkers, and discusses microbiome-modulation strategies designed to enhance immunotherapy and chemotherapy, thereby offering a complementary paradigm for CRC prevention and treatment.
OBJECTIVE:The probiotic, Bifidobacterium animalis, (B. animalis) is known to provide health benefits in humans. This study investigated the role of B. animalis in suppressing malignant melanoma progression and modulating tumor immunity. METHODS:Bifidobacterium spp. were isolated from human faeces and verified by whole-genome sequencing. The anti-tumor effects were assessed in B16-F10 melanoma cells. B. animalis efficacy was further evaluated in a syngeneic murine model. Immune profiling was performed with flow cytometry and CD8+ T cell dependency was tested with antibody depletion. Functional metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS). Transcriptome sequencing elucidated the YAP1 mechanism in CD8+ T cells. Gut microbiota composition was assessed via shotgun metagenomic sequencing. RESULTS:Among the selected Bifidobacterium spp., B. animalis and its conditioned medium effectively inhibited melanoma cell proliferation. Oral administration of B. animalis significantly reduced the growth of B16-F10 allografts, accompanied by an increase in tumor-infiltrating effector T cells. The bioactive component of B. animalis was identified as a < 3-kDa non-protein fraction containing mannose, which phenocopied the anti-tumor and immunostimulatory effects of B. animalis. Microbiota profiling revealed probiotic enrichment in mannose-treated mice. CD8+ T cell depletion abrogated mannose efficacy. Combination therapy with B. animalis and anti-PD-1 synergistically enhanced tumor control and T cell activation. Mechanistically, the bioactive fraction and mannose downregulated YAP1 expression in CD8+ T cells. CONCLUSIONS:B. animalis suppresses melanoma tumorigenesis in mice by restoring gut microbiota and secreting functional mannose. Mannose enhances anti-PD-1 efficacy by inhibiting YAP1 expression in CD8+ T cells, thereby improving effector function. B. animalis may serve as a preventive measure for melanoma management.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies of the digestive system, with a 5-year survival rate of only 13%, which is largely due to late-stage diagnosis and limited therapeutic options. Emerging evidence indicates that the gut microbiota has a critical role in PDAC tumorigenesis, progression, and therapeutic response. This review comprehensively summarizes current insights into gut microbiota-PDAC interactions, highlighting microbial alterations across taxonomic, functional, and clinical dimensions. Gut dysbiosis, which is marked by depletion of beneficial species and enrichment of pathogenic taxa, contributes to carcinogenesis through chronic inflammation, immune dysregulation, and metabolic reprogramming. In particular, the loss of butyrate-producing bacteria reduces anti-inflammatory activity and weakens CD8 + T cell function, thereby promoting tumor development. In addition to initiation, the gut microbiota also shapes PDAC progression through direct translocation to pancreatic tissue and systemic regulation of the tumor microenvironment (TME), influencing immune cell dynamics and fostering therapeutic resistance. Clinically, distinct microbial signatures are emerging as potential diagnostic and prognostic biomarkers. Moreover, microbiota-targeted interventions, including probiotics, synbiotics, fecal microbiota transplantation (FMT), metabolite supplementation, and dietary modulation, show promise as adjunctive therapeutic strategies. However, significant challenges remain in defining causal mechanisms and translating these findings into practice. Future research should integrate multi-omics profiling with well-designed clinical trials to delineate the gut microbiota-PDAC interaction network, guide precision microbiota-based interventions, and ultimately enable earlier detection and personalized treatment of this lethal disease.
Cancer immunotherapy has revolutionized oncology by harnessing the immune system to eliminate malignant cells, yet its efficacy remains constrained by insufficient antigen presentation, limited T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Nanotechnology provides strategies to address these barriers by enabling the precise delivery of antigens, adjuvants, cytokines, checkpoint inhibitors, and nucleic acids, while protecting labile cargos and allowing for controlled release. Beyond serving as carriers, nanoparticles can regulate antitumor immunity by enhancing antigen presentation, promoting T cell priming and infiltration, and remodeling the TME. This review outlines key physiological barriers to in vivo nanoparticle delivery and the corresponding engineering optimization strategies, and systematically summarizes representative advances in using nanomaterials to enhance antigen presentation, promote T cell priming and intratumoral infiltration, and remodel the tumor microenvironment. We further discuss major translational limitations, including heterogeneous tumor accumulation, intracellular trafficking bottlenecks, safety considerations, and manufacturing consistency, and finally highlight the realizable potential of nano-immunotherapy to improve both the efficacy and specificity of cancer immunotherapy.
Biomineralization is a highly regulated, multi-scale biological process that is well-characterized in physiologic contexts but remains poorly understood in pathologic settings. Tumor-associated calcification frequently occurs in clinical practice but is often regarded as an imaging feature rather than an active biological phenomenon. Existing evidence has indicated that tumor calcification is closely linked to cancer progression, prognosis, and underlying biological behavior. This review synthesizes current knowledge on tumor-associated biomineralization from a multidisciplinary perspective, integrating insights from oncology, cell biology, pathology, materials science, and systems biology. The major types and microstructural features of calcium deposition that occur in tumors are summarized and the clinical correlations are discussed. The proposed molecular and cellular mechanisms, including organelle-mediated mineral nucleation, metabolic regulation, differentiation-driven processes, and cell fate-dependent pathways, were further examined. Advances in multi-omics technologies, biomimetic models, and analytical characterization methods are highlighted as critical enablers for mechanistic investigation across biological scales. Finally, emerging strategies that exploit induced tumor calcification using engineered materials as a potential drug free therapeutic and diagnostic approach are discussed. By framing tumor calcification as an active, regulated phenotype, this review aims to provide a unified conceptual framework, identify current knowledge gaps, and encourage future research toward translational applications in cancer diagnosis and treatment.
Cancer remains one of the leading causes of morbidity and mortality worldwide.Despite substantial advances in surgery,chemotherapy,radiotherapy,targeted therapy,and immuno-therapy,effective treatment of many cancers remains challeng-ing1.
The human microbiome is increasingly recognized as a key contributor to the tumor microenvironment (TME). Advances in sequencing technologies have revealed the pivotal role of intratumoral microbiota in the development of gastrointestinal cancers. This review summarizes current knowledge on the characteristics and functional mechanisms of tumor-resident bacteria in colorectal, gastric, and hepatocellular carcinoma. We describe how these microbes affect carcinogenesis and disease progression through multiple pathways, including interactions between the microbiota and the host gut barrier, tumor cells, anti-tumor immunity, and other non-cellular components of the TME. In addition, the translational potential of intratumoral microbiota as diagnostic and prognostic biomarkers, as well as the influence on therapeutic responses, is discussed. A growing understanding of tumor-microbe interactions not only deepens insight into cancer biology but also opens new directions for innovative diagnostic and therapeutic strategies, highlighting the potential of targeting the intratumoral microbiome to improve patient outcomes in gastrointestinal oncology.
New therapies and supportive care have converted several cancer types into chronic conditions. Yet, some tumors exhibit features reproducibly correlated with poor prognosis outcome (PPO-tumors). Bacteria in a tumor environment can inactivate chemotherapeutics and are a feature of PPO-tumors, although standard diagnostic tests for tumor infections do not exist. Optimism is high for nanotechnologic innovations but nanoparticulate chemotherapeutics based on enhanced permeability and retention in a human tumor environment have only shown limited treatment benefits. Moreover, treatment of infected tumors in animals with stimuli-responsive nanocarriers loaded with an antibiotic/chemotherapeutic combination has demonstrated limited benefits compared to treatment with combinations of carrier-free antibiotics and chemotherapeutics. Development of nanoparticulate chemotherapeutics with significant benefits in human clinical use is estimated to take several decades, which is too long for patients with PPO-tumors. Herein we hypothesize the following: 1-all diagnosed PPO-tumors are infected with bacteria; 2-all PPO-tumors in mice and humans exhibit enhanced permeability to chemotherapeutics; and 3-all diagnosed PPO-tumors must be treated from the onset with a combination of carrier-free antibiotics and chemotherapeutics. Each hypothesis was critically evaluated and judged plausible and clinically acceptable. Potential clinical treatment of PPO-tumors, presuming bacterial infection without diagnosis, with an approved antibiotic and chemotherapeutic free drug combination requires a paradigm change in treatment concept towards more lenient antibiotic use. However, many cancer patients already require antibiotics during chemotherapeutic treatment and combined carrier-free antibiotic/chemotherapeutic treatment may provide an immediate pathway to re-sensitize PPO-tumors to clinically used chemotherapeutics and alter the prognosis to a more favourable outcome.
Hepatocellular carcinoma (HCC) remains a major global health challenge with limited long-term survival despite advances in surgical, locoregional, and systemic treatments. Although immune checkpoint blockade (ICB) has reshaped HCC therapy, only a subset of patients achieves durable responses, reflecting substantial heterogeneity in tumor biology and immune microenvironments. Dysbiosis, involving the loss of beneficial bacteria, like Lactobacillus reuteri and Akkermansia muciniphila, and the expansion of pathogens, such as Klebsiella pneumoniae and Catenibacterium mitsuokai, drives HCC by promoting microbial translocation and chronic inflammation. This process is mediated by microbiota-derived metabolites. Pro-carcinogenic agents, like deoxycholic acid (DCA) and quinolinic acid, induce inflammation and activate oncogenic pathways, while protective short-chain fatty acids (SCFAs), like acetate and butyrate, modulate T-cell and ILC3 responses to influence antitumor immunity. Tryptophan catabolites, acting via the aryl hydrocarbon receptor (AhR), further fine tune immune and barrier functions. In addition, emerging data implicate intratumoral microbiota as active modulators of immune suppression and metastatic behavior. These mechanistic insights have accelerated the development of microbiome-targeted interventions, such as probiotics, prebiotics, engineered bacterial strains, and fecal microbiota transplantation, to enhance ICB responsiveness. This review synthesizes current advances linking the gut microbiome to HCC immunobiology and highlights emerging therapeutic strategies aimed at optimizing immunotherapy through precise microbial modulation.
