Cancer Biology & Therapy最新文献

{"title":"Toll-like receptor 4 inhibition sensitizes non-small cell lung cancer to radiotherapy.","authors":"Ryma Haroun, Cleopatra Rutihinda, Aissatou Hadja Diallo, Juan Pablo Ordonez, Sahar Nassri, Aliya Shams, Maria Fernanda Meza Pacheco, Nour Elhouda Saidi, Lea Bouchard, Guy-Anne Turgeon, Denis Gris, Lee-Hwa Tai, Ayman J Oweida","doi":"10.1080/15384047.2025.2590881","DOIUrl":"10.1080/15384047.2025.2590881","url":null,"abstract":"<p><p>Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Although radiotherapy (RT) is used to treat over half of NSCLC patients, about 30% have inherent or acquired radioresistance leading to treatment failure. There's a clinically unmet need to investigate mechanisms of radioresistance that can be targeted in combination with RT. Among these, HMGB1 has been shown to play a key role in tumor progression. Our research investigates TLR4, a receptor for HMGB1, highly expressed in NSCLC tissues, as a mediator of radioresistance.</p><p><strong>Methods: </strong>The TLR4 inhibitor, TAK242, was tested in NSCLC cell lines (murine: LLCI, KLN205; human: H1975, SW900). Cells were irradiated at 2 and 10 Gy. <i>In vivo</i>, KLN205 cells were implanted in DBA/2 mice and tumors were irradiated at 10Gy. Gene and protein expression of TLR4 and MyD88 were assessed <i>in vitro</i> and <i>in vivo</i>. HMGB1 secretion was quantified after RT. Clonogenic assays were performed to evaluate the effect of TAK242 on radiosensitivity <i>in vitro</i>. The combination of TAK242 and RT was investigated <i>in vivo</i> in mice bearing KLN205 tumors.</p><p><strong>Results: </strong>TAK242 significantly decreased NSCLC cell proliferation and migration. Radiation at 2 and 10 Gy increased TLR4 gene expression <i>in vitro</i> and <i>in vivo</i> in a dose-dependent manner. <i>In vitro</i>, TLR4 and HMGB1 protein expression was upregulated following radiation. TAK242 in combination with radiation enhanced radiosensitivity <i>in vitro</i>. TAK242 decreased the percentage of cells in the G1 phase, coupled with an increase in late S and G2/M, suggesting radiosensitization via cell cycle modulation. <i>In vivo</i>, the combination of RT and TAK242 significantly reduced growth of KLN205 tumors.</p><p><strong>Conclusion: </strong>These findings show that TLR4 inhibition enhances RT sensitivity in NSCLC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2590881"},"PeriodicalIF":4.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12688242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel biochip-based liquid biopsy for extracellular vesicle RNA detection in prostate cancer.","authors":"Yanjun Diao, Ani Nan, Rui Li, Ting Ding, Zhuo Li, Juan Wang, Bingbing Zhu, Jinjie Li, Liu Yang, Lei Zhou, Jiayun Liu, Xiaoke Hao","doi":"10.1080/15384047.2025.2593744","DOIUrl":"10.1080/15384047.2025.2593744","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a major health concern, and current PSA screening is limited by low specificity and the risk of overdiagnosis. Extracellular vesicle (EV)-derived RNA biomarkers offer a promising non-invasive alternative for early detection.</p><p><strong>Methods: </strong>We utilized a tethered cationic lipoplex nanoparticle (TCLN) biochip for amplification-free EV RNA detection at the single-vesicle level. Eight candidate RNAs (four miRNAs, three mRNAs, and one lncRNA) were profiled in serum and urine samples from PCa patients, benign prostatic hyperplasia (BPH) patients, and healthy controls (HC). Diagnostic and risk stratification performance was evaluated in discovery and validation cohorts, with qRT-PCR used for validation.</p><p><strong>Results: </strong>TCLN reliably detected the candidate RNA biomarkers from PCa cell lines and clinical samples, with strong concordance to qRT-PCR. Serum EV RNAs (miR-141, miR-375, Let-7c) and urine EV RNAs (miR-141, miR-375, PCA3 lncRNA, T1-E2) effectively distinguished PCa patients from controls. Combined EV RNA biomarkers in serum and urine achieved diagnostic area-under-the-curve (AUCs) of 0.824 and 0.741, respectively, surpassing those of prostate-specific antigen (PSA) alone. Serum miR-141, miR-375, and urine miR-141, miR-375, and PCA3 lncRNA, also showed remarkable correlations with PCa Gleason score (GS), tumor stage, and metastatic status.</p><p><strong>Conclusion: </strong>The TCLN biochip enables sensitive, amplification-free detection of EV RNA biomarkers from serum and urine. Key markers such as miR-141, miR-375, and PCA3 showed strong diagnostic and risk stratification value in PCa. This non-invasive approach holds promise for improving early detection and clinical risk assessment.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2593744"},"PeriodicalIF":4.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12688251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cGAS-STING signaling in the tumor microenvironment induces myeloid cell activation and favors T cell-mediated antitumor immunity.","authors":"Meiqi Ren, Zhichao Eric Ai, Yan Zhang, Linghong Shi, Yafei Liu, Haixia Liu, Hong Shen, Xiangyu Yao, Zhipeng Yan","doi":"10.1080/15384047.2025.2585562","DOIUrl":"10.1080/15384047.2025.2585562","url":null,"abstract":"<p><p>The cancer-immunity cycle is regulated by a series of stimulatory and inhibitory factors. The stimulator of interferon genes (STING) pathway, a key stimulator of type I interferon production, connects innate and adaptive immunity to promote antitumor responses. Using a syngeneic pancreatic tumor model, we characterized the single-cell landscape changes induced by STING stimulation. Our findings revealed that STING agonist treatment reprograms transcription across multiple cell lineages, enhances innate immune responses and activates lymphocytes, thereby promoting antitumor effects. Single-cell transcriptome sequencing identified significant increases in monocytes, neutrophils, macrophages, and CD8 T cells, indicating augmented tumor inflammation. Differential gene expression analysis highlighted upregulated genes related to immune cell effector mechanisms and antigen presentation. Functional assays confirmed the enhanced tumor killing effects induced by STING activation. These results underscore the potential of STING agonists in reprogramming the tumor microenvironment to potentiate antitumor immunity, although clinical translation remains challenging owing to pharmacokinetic limitations and potential systemic toxicity. Further research is needed to optimize STING agonist delivery and dosage for effective cancer immunotherapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2585562"},"PeriodicalIF":4.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12667634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and caveats in manipulating extracellular vesicle secretion from pancreatic cancer cells.","authors":"Jennifer M Finan, Jonathan R Brody","doi":"10.1080/15384047.2025.2569946","DOIUrl":"10.1080/15384047.2025.2569946","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicle (EV) signaling is important in multiple malignancies, including pancreatic ductal adenocarcinoma (PDAC). In this coordinated cell‒cell signaling mechanism, genetically altered tumor cells signal to surrounding normal cells to promote tumor progression. Many efforts have been made to mechanistically interrogate this signaling axis by inhibiting EV secretion from cells. These techniques leverage our understanding of how EV biogenesis interferes with ceramide production or GTPase activity, which aids in membrane fusion with the plasma membrane.</p><p><strong>Material and methods: </strong>Our group leveraged these methods in our orthotopic PDAC mouse model to investigate the importance of PDAC EV secretion. We interfered with the GTPases Rab27a and Rab35 and utilized an inhibitor of ceramide production (GW4869) to ablate EV secretion.</p><p><strong>Results and conclusion: </strong>Overall, we found that these models did not perform as anticipated, and we could not consistently inhibit KPC cell EV secretion. These results emphasize the challenges of interfering with EV secretion, as several parallel pathways, such as direct membrane budding, can compensate. Further studies are needed to develop models for studying the role of EVs <i>in vivo</i>.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2569946"},"PeriodicalIF":4.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12562733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear translocation of Cx43 promotes to CRC progression and associates with β-catenin accumulation.","authors":"Shuo Wang, Ziling Zhu, Yin Zhu, Jing Tan, Xiujin Shen, Huan Wen, Jian Wu, Jingyao Xu, Jiangjiang Zheng, Yuhan Chen, Wanxi Yang, Hong Deng","doi":"10.1080/15384047.2025.2589645","DOIUrl":"10.1080/15384047.2025.2589645","url":null,"abstract":"<p><strong>Background: </strong>The tumour microenvironment (TME) significantly influences intercellular communication, with several secreted factors activating both tumour cells and fibroblasts. Connexin43 (Cx43), a crucial gap junction protein, exhibits a significant regulatory role in tumourigenesis; however, the underlying regulatory mechanisms in colorectal cancer (CRC) are not fully understood.</p><p><strong>Methods: </strong>Transwell co-culture system was utilized to evaluate fibroblast-mediated effects on CRC cells. Immunohistochemical analysis was conducted on clinical specimens. Cell migration and invasion capabilities were measured using Transwell assays. Subcellular localization was assessed via immunofluorescence. Protein interactions were validated by co-immunoprecipitation.</p><p><strong>Results: </strong>The Wnt signalling pathway was activated in the co-culture of CRC cells and fibroblasts. Nuclear Cx43 upregulation was detected and confirmed as a pro-oncogenic factor via prognostic analysis of patient samples. Therefore, although Cx43 on the cell membrane serves as a tumour suppressor, the nuclear translocation of Cx43 has an important influence on the Wnt signalling pathway and promotes CRC progression. Nuclear translocation of Cx43 during malignant progression has a significant effect on metastasis and is regulated by secreted TGF-<i>β</i>. Distinct nuclear translocation patterns of Cx43 observed across CRC cell lines suggest potential regulation by S368 phosphorylation. Co-immunoprecipitation confirmed Cx43/β-catenin interaction, revealing its role in facilitating <i>β</i>-catenin nuclear accumulation.</p><p><strong>Conclusion: </strong>We systematically identified nuclear Cx43 as a factor promoting CRC progression. These findings highlight the novel mechanism involving the nuclear translocation of Cx43 as a promoting factor in CRC progression, and enhance our understanding of the interplay between the TME and CRC progression.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2589645"},"PeriodicalIF":4.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12688224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2025.2602376","DOIUrl":"10.1080/15384047.2025.2602376","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2602376"},"PeriodicalIF":4.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12721083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2025.2500190","DOIUrl":"https://doi.org/10.1080/15384047.2025.2500190","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2500190"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of cell death pathways in three different kinds of human lung cancer cell lines following hematoporphyrin derivative-mediated photodynamic therapy.","authors":"Yijiang Ma, Baohong Xiao, Aihua Sui, Xiaohui Yang, Shichao Cui, Yiwei Cao, Cunzhi Lin","doi":"10.1080/15384047.2025.2542011","DOIUrl":"10.1080/15384047.2025.2542011","url":null,"abstract":"<p><p>This study was conducted to investigate the in vitro differences in killing effects and cellular death pathways in human bronchial epithelial BEAS-2B cells, human lung adenocarcinoma A549 cells, human lung squamous carcinoma H520 cells, and human lung small cell carcinoma H446 cells mediated by hematoporphyrin derivative (HPD) at 630 nm laser wavelength. Our results showed that the viability of the BEAS-2B, A549, H520, and H446 cells gradually decreased with increasing HPD concentration after HPD-PDT. HPD-PDT induced an increase in intracellular ROS production (<i>p</i> < 0.05), with H520 > A549 > H446 > BEAS-2B. HPD-PDT resulted in intracellular chromatin fixation and dense nuclear staining and induced apoptosis, with apoptosis rates of H520 > A549 > H446 > BEAS-2B. The western blotting (WB) results showed that HPD-PDT could lead to reduced BCL-2 protein levels, upregulate BAX protein expression and activate caspase-3 protein, and induce autophagy, as evidenced by the increased expression of the autophagy-related proteins ATG5, Beclin-1 and LC3B in all cells tested. However, apoptosis-inducing proteins and autophagy proteins were statistically different in these four cell types. Our study confirms that HPD-mediated phototoxicity varied in the different cell lines, indicating that lung cancer cells die due to the interactions of different cell death pathways rather than the same well-defined mechanisms.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2542011"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-Derived Exosomes: mediators of crosstalk between Adipose tissue and cancer.","authors":"Changjian Wang, Zhikun Zheng, Chuangyan Wu, Dan Zhang, Yangchenxi Wang, Sheng Zhang, Geng Wang, Rui Zhou","doi":"10.1080/15384047.2025.2547564","DOIUrl":"10.1080/15384047.2025.2547564","url":null,"abstract":"<p><p>Adipose-derived exosomes (ADEs), a subtype of extracellular vesicles, are critical mediators of communication between adipose tissue and tumors, playing pivotal roles in cancer progression and therapeutic response. These nanoscale vesicles carry microRNAs, proteins, and lipids that influence tumor cell proliferation, migration, metastasis, and immune modulation. The dual functions of ADEs - both in promoting and suppressing tumorigenesis - are largely dependent on their cellular origin, molecular cargo, and the characteristics of the tumor microenvironment. Recent studies have identified ADEs as potential diagnostic biomarkers, therapeutic targets, and drug delivery platforms, offering promising avenues for precision oncology. However, significant challenges - such as biological heterogeneity, lack of standardization in production, concerns regarding efficacy and safety, and regulatory constraints - continue to hinder their clinical translation. This review aimed to explore the multifaceted roles of ADEs in cancer pathogenesis, their therapeutic potential, and current limitations, providing insights to guide future research and clinical applications.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2547564"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the dual role of METTL3-mediated m⁶A RNA modification in bladder cancer: mechanisms, therapeutic vulnerabilities, and clinical implications.","authors":"Hua Chun, Kangzhuo Baima","doi":"10.1080/15384047.2025.2545057","DOIUrl":"10.1080/15384047.2025.2545057","url":null,"abstract":"<p><p>Bladder cancer (BC) remains challenging due to its recurrence and metastasis, with METTL3-mediated m⁶ A RNA modification emerging as a key oncogenic driver. This review synthesizes METTL3's roles in BC progression, including tumor initiation, metastasis, stemness, and therapy resistance. We detail its regulation of critical pathways (e.g. HIF1A/IGF2BP3/BIRC5, AFF4/NF-κB/c-MYC) and dual functions in RNA stability and epigenetic crosstalk with DNA methylation. METTL3 promotes chemoresistance (e.g. circ0008399/WTAP/TNFAIP3) and immune evasion (PD-L1 stabilization), while its overexpression correlates with poor prognosis and cisplatin resistance. By integrating METTL3's interactions with m⁶ A readers (YTHDF1/2, IGF2BP3) and erasers (ALKBH5), we propose targeting METTL3 as a strategy to enhance chemotherapy and immunotherapy efficacy. This work underscores METTL3's potential as a diagnostic biomarker and therapeutic target, advancing precision oncology in BC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2545057"},"PeriodicalIF":5.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}