Cancer Biology & Medicine最新文献

{"title":"FDX1 expression promotes DSF/Cu-induced cuproptosis in gastric cancer cells.","authors":"Qirong Li, Yi Guo, Jiahuan Yuan, Qiang Feng, Hengzong Zhou, Ming Hao, Boqiang Tao, Liqun Sun, Chao Lin, Jianfeng Mu, Gongliang Guo, Dongxu Wang","doi":"10.20892/j.issn.2095-3941.2025.0323","DOIUrl":"10.20892/j.issn.2095-3941.2025.0323","url":null,"abstract":"<p><strong>Objective: </strong>Gastric cancer (GC) is a prevalent malignant tumor that warrants the development of drugs and therapeutic targets. Cuproptosis has emerged as a promising mechanism by which to inhibit tumors because copper homeostasis disorders frequently occur in various malignancies. The combination of disulfiram (DSF) and copper ions (DSF/Cu) has been shown to have significant antitumor effects. This study utilized DSF/Cu to investigate the mechanism underlying cuproptosis in GC cells.</p><p><strong>Methods: </strong>GC cells were treated with DSF/Cu and protein sequencing was performed to screen for differentially expressed genes. The mechanism by which overexpressed <i>FDX1</i> regulates cuproptosis and <i>WDR43</i> expression was determined. Subsequently, how to improve the efficacy of DSF/Cu in the treatment of GC was studied in a mouse model of GC.</p><p><strong>Results: </strong>DSF/Cu had a good therapeutic effect on promoting cuproptosis in GC cells. Protein sequencing revealed <i>WDR43</i> as a downstream gene of <i>FDX1</i>. Increasing the expression of <i>FDX1</i> enhanced the sensitivity of GC cells to copper treatment and inhibited the expression of <i>WDR43</i>, thereby exerting an antitumor effect. Furthermore, DSF/Cu was loaded into exosomes derived from natural killer (NK) cells to enhance the biological safety and tumor targeting of DSF/Cu and validate the inhibitory effect on GC both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Conclusions: </strong>This study showed that DSF/Cu promoted cuproptosis and the expression of <i>FDX1</i> affected cuproptosis sensitivity of GC. Moreover, the combination of NK cell exosomes with DSF/Cu improved the therapeutic effect of DSF/Cu, which helps to promote the targeted therapy of GC and improve clinical applicability.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid cell reprogramming combined with zoledronic acid effectively suppresses bone metastasis.","authors":"Yuting Luo, Yiran Cai, Zizheng Jiang, Ke Zheng, Shiji Ren, Lixia Yu, Baorui Liu, Tao Shi, Jia Wei","doi":"10.20892/j.issn.2095-3941.2026.0168","DOIUrl":"10.20892/j.issn.2095-3941.2026.0168","url":null,"abstract":"<p><strong>Objective: </strong>Bone metastases are refractory to current therapies, primarily owing to the immunosuppressive metastasis tumor microenvironment (TME), which is dominated by myeloid cells. However, the function and regulatory mechanisms of myeloid compartments within the bone TME are incompletely understood. Herein we sought to delineate the role of the DKK1-CKAP4 axis in shaping myeloid cell-mediated immunosuppression in bone metastases and to identify potential therapeutic strategies targeting this pathway.</p><p><strong>Methods: </strong>The composition and phenotypic characteristics of myeloid cells in the bone TME were analyzed. Mechanistic studies were conducted using <i>ex vivo</i> co-culture systems and an <i>in vivo Ckap4</i>^fl/fl<i>S100a8</i>^Cre (neutrophil-specific <i>Ckap4</i> knockout) mouse model to delineate the role of the DKK1-CKAP4 axis in regulating neutrophil maturation, osteoclast-like cell differentiation, and macrophage polarization. The therapeutic efficacy of DKK1 blockade in combination with zoledronic acid, as well as the impact on remodeling the TME, was further validated in bone metastasis mouse models.</p><p><strong>Results: </strong>Significant expansion and predominance of myeloid cells within the bone TME was noted. Mechanistically, the DKK1-CKAP4 axis regulated the development and function of multiple myeloid populations. The DKK1-CKAP4 axis drove neutrophils toward an immature-like, immunosuppressive phenotype, promoted osteoclast-like cell differentiation, and induced macrophage polarization into an M2-like phenotype. Importantly, combined therapy with DKK1 blockade and zoledronic acid reprogrammed immunosuppressive myeloid cells, restored antitumor immunity, and significantly reduced tumor burden in bone metastasis models.</p><p><strong>Conclusions: </strong>The findings herein showed the DKK1-CKAP4 axis to be a key regulator of myeloid-driven immunosuppression in the bone TME. The combination of DKK1 blockade with zoledronic acid represents a potential therapeutic strategy for bone metastases.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From chemical compounds to herbal interventions: a transfer learning-based perturbational transcriptome prediction framework for cancer drug discovery.","authors":"Qingyuan Liu, Boyang Wang, Shao Li","doi":"10.20892/j.issn.2095-3941.2026.0032","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2026.0032","url":null,"abstract":"<p><strong>Objective: </strong>Transcriptomic perturbation profiles from tumor cell lines serve as the core molecular basis for cancer drug discovery and mechanism of action (MOA) analysis. Traditional Chinese medicine (TCM) holds great anticancer potential, yet the multi-component and multi-target properties pose major challenges for systematic mechanistic investigation. The scarcity of herbal intervention transcriptomic data severely restricts transcriptome-based anticancer TCM research, unlike widely available large-scale chemical compound perturbational datasets. This study aims to establish a predictive framework for herbal transcriptional responses in tumor cell models to address this critical data bottleneck.</p><p><strong>Methods: </strong>A transfer learning-based encoder-decoder prediction framework integrated with a self-attention mechanism was developed. The model was pre-trained on large-scale connectivity map compound perturbation datasets with paired baseline transcriptomic profiles, then fine-tuned with limited herbal perturbation data covering 11 herbs across 4 tumor cell lines using a shared gene set as the molecular basis.</p><p><strong>Results: </strong>The model achieved strong predictive performance (mean squared error = 0.1395, R² = 0.8561, Pearson correlation coefficient = 0.9258), outperforming baseline models with robust generalization to unseen herbal interventions. Transfer learning markedly improved prediction accuracy and stability under data-limited conditions.</p><p><strong>Conclusions: </strong>This framework provides a scalable, cost-effective computational approach for anticancer herbal <i>in silico</i> screening, preliminary MOA exploration, and multi-herb prescription synergistic pattern analysis in cancer drug discovery.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global patterns, temporal trends and socioeconomic inequalities in the burden of breast cancer: a population-based study across 185 countries.","authors":"Weijia Kong, Hengna Lin, Jie Li, Yaxiong Nie, Rongshou Zheng, Di Liang","doi":"10.20892/j.issn.2095-3941.2026.0059","DOIUrl":"10.20892/j.issn.2095-3941.2026.0059","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation CAR immunotherapy for neuroblastoma: expanding the role of immune cell platforms.","authors":"Ke-En Tan, Kok Siong Yeo, Yat-Yuen Lim, Shizhen Zhu","doi":"10.20892/j.issn.2095-3941.2026.0155","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2026.0155","url":null,"abstract":"<p><p>Neuroblastoma (NB) is a pediatric cancer that develops from immature nerve cells in the peripheral sympathetic nervous system. NB is remarkably heterogeneous, ranging from spontaneous regression to aggressive progression, and is characterized by widespread dissemination and relapse. Approximately half of all NB patients present with widespread metastasis at diagnosis and are classified as high-risk with a substantial likelihood of treatment failure, despite receiving aggressive multimodal therapies, including surgery, chemotherapy, radiotherapy, autologous hematopoietic stem cell transplantation, and monoclonal antibody treatment. Beyond conventional multimodal approaches, immunotherapy has emerged as an essential part of cancer treatment, by boosting the immune system to recognize and eliminate tumor cells. In this review, we provide an overview of current therapeutic strategies for NB patients and summarize recent advances in the development of next-generation NB immunotherapies, highlighting their potential to improve NB management. We further discuss future directions for therapeutic improvement, and the potential limitations and challenges associated with translating these approaches into long-term benefits for NB patients.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apatinib enhances targeted immunotherapy <i>via</i> the IL-6-gp130-PI3K pathway in HER2-positive gastric cancer.","authors":"Ruoxi Tian, Ziyue Sha, Shasha Zhang, Miao Gong, Jianhua Wu, Juntao Lu, Wei Guo, Zhaoxu Zheng, Zhanjun Guo","doi":"10.20892/j.issn.2095-3941.2025.0687","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2025.0687","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to evaluate chemotherapy-free apatinib-based immunotherapy regimens for patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) who were chemotherapy-intolerant or declined chemotherapy.</p><p><strong>Methods: </strong>Enriched KEGG/GO pathway analyses were used to identify pathways modulated by apatinib treatment and those associated with trastuzumab sensitivity. RNA-seq data from TCGA were used to evaluate interleukin-6 (IL-6)'s role in HER2-positive GC. The efficacy of combination therapy was validated in HER2-positive GC cell lines, humanized hematopoietic stem cells, tumor cell line-derived xenografts (hHSC-CDXs), and 3 patients with stage IV GC. Mechanistic studies involved co-immunoprecipitation, western blotting, immunohistochemistry, and immunofluorescence assays.</p><p><strong>Results: </strong>Apatinib enhanced the trastuzumab-induced inhibition of HER2-positive GC by blocking the IL-6/glycoprotein 130 (gp130)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/signal transducer and activator of transcription 3 (STAT3) signaling pathway <i>in vitro</i>, as validated through bioinformatics analysis. We confirmed the synergistic effects of apatinib with the targeted immunotherapy combination in inhibiting HER2-positive GC in both hHSC-CDXs and patients with HER2-positive GC. Given that apatinib suppressed HER2-positive GC <i>via</i> IL-6, we also confirmed that tocilizumab (a monoclonal antibody targeting IL-6R) significantly potentiated apatinib's efficacy with targeted immunotherapy in hHSC-CDXs. Potential mechanisms of immunotherapy enhancement with apatinib and tocilizumab included decreased angiogenesis, M2-like tumor-associated macrophages (M2-TAMs), and regulatory T cells (Tregs), as well as increased cytotoxic CD8⁺ T cell infiltration in the tumor microenvironment.</p><p><strong>Conclusions: </strong>Our data support the potential application value of tocilizumab and apatinib for targeted immunotherapy in patients with HER2-positive GC, particularly in older patients who cannot tolerate chemotherapy.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the microbiome: a new frontier in lung cancer immunotherapy.","authors":"Kexin Feng, Jun Wang, Shuai Wang, Zewen Sun, Mantang Qiu, Zuli Zhou, Yun Li, Kezhong Chen","doi":"10.20892/j.issn.2095-3941.2025.0177","DOIUrl":"10.20892/j.issn.2095-3941.2025.0177","url":null,"abstract":"<p><p>Lung cancer is a fatal and the most common malignancy globally. Despite the significant therapeutic benefits of immune checkpoint inhibitors (ICIs), 60%-80% of patients respond poorly to immunotherapy. The identification of reliable predictive biomarkers is essential for implementing precision medicine strategies. In recent years the microbiome has emerged as a promising predictor of immunotherapy outcomes. The influence of the microbiome on lung cancer immunotherapy was systematically and comprehensively reviewed. Moreover, the distinctive microbiome profiles among patients with lung cancer and the correlation with treatment effectiveness are discussed. We investigated the core mechanisms of the interactions between the microbiome and the tumor microenvironment, assessed the usefulness of microbial metabolites as predictive biomarkers, and discussed strategies for microbiome-targeted interventions. Furthermore, we evaluated the current limitations in research methodology and highlighted future research directions, offering novel insights, including multi-site integrated biomarker approaches, site-specific intervention strategies, metabolite-based functional biomarkers, and lung cancer-specific microbiome considerations for developing personalized immunotherapy.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic susceptibility, environmental risk factors, and incident gastric cancer risk among individuals with different <i>Helicobacter pylori</i> infection status: a population-based study.","authors":"Hengmin Xu, Hui Ma, Yuxin Wang, Xinling Wang, Xuan Han, Wenjing Zhao, Yang Zhang, Tong Zhou, Jingying Zhang, Weicheng You, Wenqing Li, Kaifeng Pan","doi":"10.20892/j.issn.2095-3941.2026.0145","DOIUrl":"10.20892/j.issn.2095-3941.2026.0145","url":null,"abstract":"","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary restriction during active cancer therapy is associated with improved treatment response: a systematic review and meta-analysis.","authors":"Kajal Agrawal, Dominic Shao Yong Goh, Ee Chern Ng, Shyn Yi Tan, Carlos Cifuentes-González, Jason Xing Kang, William K K Wu, Rashid N S Lui, Rupesh Agrawal, Yusuf Ali, Sunny H Wong","doi":"10.20892/j.issn.2095-3941.2025.0841","DOIUrl":"10.20892/j.issn.2095-3941.2025.0841","url":null,"abstract":"","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The conditional promise of dual-epitope HER2 antibody-drug conjugates in breast cancer.","authors":"Ruoqing Wang, Shuhao Jiang, Qun Zhang, Junjie Li","doi":"10.20892/j.issn.2095-3941.2026.0277","DOIUrl":"10.20892/j.issn.2095-3941.2026.0277","url":null,"abstract":"","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}