Medical Oncology最新文献

{"title":"Metamizole limits proliferation in chronic myeloid leukemia cells and triggers apoptosis via the bax/bcl-2/caspase-3 cascade.","authors":"Erkan Maytalman, Dilara Nemutlu Samur","doi":"10.1007/s12032-025-02842-x","DOIUrl":"10.1007/s12032-025-02842-x","url":null,"abstract":"<p><p>Metamizole is a controversial non-steroidal anti-inflammatory drug because it may cause agranulocytosis usually in long-term use. It may reduce proliferation while increasing apoptosis in some cancer cells. In our study, the effects of increasing concentrations of metamizole on chronic myeloid leukemia (CML) cell line K562 were evaluated in terms of proliferation and apoptosis. K562 cells were cultured with 1,10,50,100 µM concentrations of metamizole in addition to the control group. The effect on cell proliferation was determined by MTT and analysis of mitotic cell counts. The apoptotic effects were analyzed by flow cytometry using Annexin V/Propidium iodide, ELISA for caspase-3 concentrations, and RT-qPCR for Bax-Bcl-2 mRNA expression levels. Evaluations were performed for 24 and 48 h of exposure. MTT assay revealed that metamizole limited the proliferation of cells at 10 µM concentration. Caspase-3 concentrations increased in cells exposed to concentrations of 50 µM and above. Flow cytometry results obtained using Annexin V/PI showed that especially 50 and 100 µM concentrations promoted apoptosis compared to the control. Bcl-2 mRNA expression was also significantly decreased at concentrations of 50 and 100 µM, while Bax mRNA expression was significantly increased only for 100 µM. Mitotic cell numbers also decreased with increasing concentrations. The known adverse effect of metamizole, agranulocytosis, suggests it may negatively affect cell proliferation. In this study, metamizole had both antiproliferative and pro-apoptotic effects on K562. The results of our study indicate that the synergistic effects of metamizole in the treatment of CML, especially in cases resistant to tyrosine kinase inhibitors, should be evaluated with further studies under in vitro and in vivo conditions.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"288"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506408","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":"Emerging roles and clinical perspectives of long noncoding RNAs in prostate cancer.","authors":"Rajarethinam Kumar, Saradhadevi Muthukrishnan","doi":"10.1007/s12032-025-02859-2","DOIUrl":"https://doi.org/10.1007/s12032-025-02859-2","url":null,"abstract":"<p><p>Prostate cancer (PCa) is one of the most frequent cancers in males and one of the leading causes of cancer-related deaths globally. Despite advances in diagnosis and treatment, PCa continues to pose substantial hurdles, especially due to its potential to evolve into more aggressive and treatment-resistant types. Long noncoding RNAs (lncRNAs) are transcripts with more than 200 nucleotides that do not encode proteins and have been identified as pivotal regulators in PCa. They influence crucial cellular mechanisms such as cell cycle control, gene expression, and translation, and their dysregulation is linked to tumour growth, progression, and metastasis. Furthermore, lncRNAs modulate androgen receptor (AR) signalling and act as competitive endogenous RNAs (ceRNAs), sequestering microRNAs to alter target gene expression, therefore driving tumour progression. This review uniquely integrates recent advances in understanding the lncRNA-mediated regulatory networks, highlighting their roles in epigenetic, post-transcriptional regulations and key signalling pathways in PCa. It also underscores the emerging clinical applications of lncRNAs as predictive biomarkers and therapeutic targets, with a focus on personalised medicines. Despite the challenges posed by patient heterogeneity and lncRNAs' complex regulatory networks, ongoing research into lncRNAs holds the promise for improving early diagnosis and advancing the development of more effective, personalised therapeutic strategies. Collectively, this review summarises the current knowledge on growing roles of lncRNAs in PCa pathogenesis, clinical relevance and their therapeutic potential and provides potential insights and future directions for translating lncRNA research into effective clinical applications.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"289"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal polyps: pathophysiology, malignant potential, and advancements in therapeutic strategies.","authors":"Anna E Kotula, Yash V Korde, Hayden J Oyler, Mark R Wakefield, Yujiang Fang","doi":"10.1007/s12032-025-02861-8","DOIUrl":"https://doi.org/10.1007/s12032-025-02861-8","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is among the most common causes of cancer-associated death. The American Cancer Society predicts a significant increase in both the incidence and mortality of CRC over the next decade for individuals 54 years or younger. This prediction underscores the urgent need for effective screening and management strategies. CRC is the third most common type of non-skin cancer in both men (after prostate and lung cancer) and women (after breast cancer and lung cancer). In 2025, it is predicted that 693,452 people will be diagnosed with metastatic colorectal cancer. Colon polyps from both an adenoma and a serrated polyp have a significant risk of developing into CRC. This is why it is essential to correctly identify and manage sessile serrated lesions to help improve the quality and reliability of screening colonoscopy. The frequency of colonoscopies is determined by the size, number, and type of polyp found. If 1-2 polyps < 1 cm in size are removed, a colonoscopy in 5 years is appropriate. If the patient had 3-4 polyps < 1 cm in size or one polyp > 1 cm removed, a colonoscopy in 3 years is recommended. If five or more small or three or more large polyps are removed, then a 1-year colonoscopy is appropriate. To prevent colon cancer, it is recommended that patients get regular screening to help prevent and detect it. Some of the treatment options include laparoscopic and robotic surgical procedures, transanal minimally invasive surgery (TAMIS), hyperthermic intraperitoneal chemotherapy (HIPEC) surgery, and Intraoperative radiation therapy (IORT). Reviewing the previous literature on the management of colorectal adenomatous polyps and colorectal cancer, it becomes apparent that the various polyps need to be thoroughly categorized, and colorectal cancer needs to be screened for effectively, and then a proper management course needs to be set in place to maximize positive patient outcomes. Such a study will be very helpful for colorectal cancer specialists to manage patients with colorectal adenomatous polyps and colorectal cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"287"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrogallol induces apoptosis, oxidative stress and cell cycle arrest in C6 glioma cells: a potential therapeutic agent.","authors":"Kamalesh Balakumar Venkatesan, Manoj Kumar Srinivasan, Monisha Prasad, Nivedha Jayaseelan, Saravanan Alamelu, Chellasamy Panneerselvam, Mohammed A Al-Duais, Abdulrahman Alasmari, Mohammad Rehan Ajmal, Hatem A Al-Aoh","doi":"10.1007/s12032-025-02835-w","DOIUrl":"https://doi.org/10.1007/s12032-025-02835-w","url":null,"abstract":"<p><p>Gliomas represent one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic strategies. Pyrogallol, a naturally occurring polyphenol, has been reported to exhibit anticancer properties, but its effects on glioma cells remain underexplored. This study investigates the cytotoxic, apoptotic and oxidative stress-inducing effects of pyrogallol on C6 glioma cells. Using MTT assays, pyrogallol demonstrated a significant dose and time dependent cytotoxicity in C6 cells, with IC50 values decreasing from 40 µM at 24 h to 15 µM at 72 h. Morphological analyses through AO/EtBr and DAPI staining confirmed apoptosis induction, showing nuclear fragmentation and membrane blebbing in treated cells. Pyrogallol also increased intracellular reactive oxygen species (ROS) and disrupted mitochondrial membrane potential (MMP), indicating oxidative stress and mitochondrial dysfunction. Flow cytometry with Annexin V-FITC/PI staining revealed a dose-dependent increase in early and late apoptotic populations, accompanied by a significant G0/G1 phase cell cycle arrest. Biochemical assays showed elevated lipid peroxidation and reduced antioxidant enzyme activities (SOD and catalase), further supporting oxidative stress involvement. At the molecular level, qRT-PCR and ELISA analyses demonstrated upregulation of pro-apoptotic genes and proteins Bax and cytochrome c, with downregulation of the antiapoptotic marker Bcl-2, confirming pyrogallol role in promoting apoptotic pathways. These findings highlight pyrogallol's potent anticancer effects on C6 glioma cells via apoptosis induction, oxidative stress, and cell cycle arrest, suggesting its potential as a therapeutic candidate against glioma.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"290"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the immune responses: a new frontier in Ewing sarcoma treatment.","authors":"Diya S Patel, Riddhi T Desai, Aanshi J Pandya, Nirjari R Kothari, Rajanikant Patel, Mehul R Chorawala","doi":"10.1007/s12032-025-02848-5","DOIUrl":"https://doi.org/10.1007/s12032-025-02848-5","url":null,"abstract":"<p><p>Ewing sarcoma (ES) is a rare and highly aggressive bone and soft tissue malignancy predominantly affecting children and young adults. It poses significant challenges in treatment due to its propensity for metastasis and resistance to conventional therapies. Despite advancements in multimodal treatment, which includes chemotherapy, surgery, and radiotherapy, outcomes remain poor for patients with metastatic or recurrent disease. Therefore, novel therapeutic strategies are urgently required. Among these, immune-based therapies have emerged as a promising frontier. This review provides an in-depth analysis of current and emerging immunotherapeutic approaches in ES, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, engineered T-cell receptor (TCR) therapy, and cancer vaccines. Preclinical studies have demonstrated the potential of these strategies, particularly in overcoming challenges related to immune evasion and targeting tumor-specific antigens. Furthermore, this article discusses the role of key components in the tumor microenvironment, such as tumor-associated macrophages, fibrocytes, and extracellular vesicles, in promoting tumor progression and immune suppression. The review also highlights completed and ongoing clinical trials that evaluate various immunotherapies for ES, shedding light on their efficacy and safety profiles. Despite encouraging progress, several obstacles remain, including limited response rates, resistance mechanisms, and adverse effects. To overcome these challenges, combination therapies, targeting both the tumor and its microenvironment, may hold promise. By summarizing current advances and future directions, this review underscores the potential of immunotherapy to improve outcomes for ES patients. Continued research into innovative immune-based strategies is crucial to achieving durable responses and long-term survival in this hard-to-treat malignancy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"291"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET3 facilitates bladder cancer progression through targeted modulation of stemness pathways.","authors":"Zhiren Cai, Yanqi Xie, Luyao Li, Yuhang Zheng, Xianghui Zhou, Guanghua Zhou, Ganping Wang, Xin Zeng","doi":"10.1007/s12032-025-02857-4","DOIUrl":"https://doi.org/10.1007/s12032-025-02857-4","url":null,"abstract":"<p><p>Bladder cancer is a major health concern, and understanding its molecular mechanisms is essential for developing effective therapies. TET3, a DNA hydroxymethylase, has been linked to tumor progression, but its role in bladder cancer remains unclear. We analyzed single-cell RNA sequencing data and identified TET3 as a key regulator in tumor-promoting cells using scissor analysis. Functional experiments were performed to evaluate the effects of TET3 knockdown on cell proliferation, migration, and gene expression. In vivo tumor growth assays and histological analyses were conducted to assess the role of TET3 in tumor progression. Additionally, we assessed the impact of TET3 on stemness-associated gene expression and performed sphere formation assays to evaluate tumor cell self-renewal capacity. TET3 was highly expressed in tumor-promoting cells. Its knockdown significantly reduced cell proliferation, migration, and tumor growth in vivo. Tumors with TET3 knockdown had lower volumes, weights, and Ki67-positive cells. Mechanistically, TET3 regulated key tumor-related genes and pathways and reduced DNA 5hmC levels. Notably, TET3 knockdown downregulated multiple stemness-related transcription factors such as SOX2 and NANOG, and impaired sphere-forming efficiency, suggesting its essential role in maintaining cancer cell stemness. This study reveals that TET3 promotes tumor growth and progression in bladder cancer partly through modulation of the stemness pathway, highlighting its potential as a therapeutic target and prognostic marker.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"284"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer potential of daidzin: a comprehensive literature review.","authors":"Md Torequl Islam, Md Tahmidur Rahman, Emon Mia, Hossam Kamli, Ali Mohamod Wasaf Hasan, Mohammed Burhan Uddin, Md Abu Sayeed, Akayed Hasan, Yasin Emon, Noshin Tasnim Yana, Mst Sumaia Akter, Rakib Hossan, Md Sakib Al Hasan, Md Shimul Bhuia","doi":"10.1007/s12032-025-02839-6","DOIUrl":"https://doi.org/10.1007/s12032-025-02839-6","url":null,"abstract":"<p><p>Daidzin (DZN), a naturally occurring isoflavone extracted from leguminous plants such as soybeans, has gained significant attention for its anticancer properties. This study provides a comprehensive overview of the pharmacokinetics (PKs), botanical sources, and therapeutic potentials of DZN, focusing on its mechanistic insights into cancer prevention and treatment. For the study, data were collected from databases such as PubMed, Google Scholar, Web of Science, and other reputable sources. In results, DZN induces oxidative stress, apoptosis, cytotoxicity, and cell cycle arrest while inhibiting proliferation, migration, invasion, and angiogenesis across various cancer cell lines, including breast, prostate, cervical, hepatocellular, and colon cancers. Its anticancer efficacy is mediated through modulation of key pathways: Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), which promotes inflammation and survival; Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), essential for proliferation and immune evasion; and Rat Sarcoma virus/Rapidly Accelerated Fibrosarcoma (RAS/RAF), a critical regulator of cell growth and chemoresistance. By inhibiting these pathways, DZN enhances apoptosis and chemotherapy sensitivity. Additionally, DZN's pharmacokinetic profile reveals favorable absorption, distribution, metabolism, and excretion (ADME) properties, with minimal toxicity in preclinical studies. Its ability to modulate pathways and enhance chemotherapy sensitivity positions DZN as a potential therapeutic candidate. Despite promising preclinical findings, the lack of clinical validation underscores the need for well-designed human trials to confirm its efficacy and safety, paving the way for its translational application in oncology.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"285"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the role of perineural invasion in cancer progression across multiple tumor types.","authors":"Muqtada Shaikh, Sanket Shirodkar, Gaurav Doshi","doi":"10.1007/s12032-025-02855-6","DOIUrl":"https://doi.org/10.1007/s12032-025-02855-6","url":null,"abstract":"<p><p>Perineural invasion (PNI) refers to the infiltration of tumor cells into the connective tissue of nerves and is increasingly recognized as a pathological hallmark of multiple cancers, including pancreatic, prostate, colorectal, breast, and head and neck malignancies. PNI is associated with aggressive tumor behavior, an increased risk of recurrence, and poor patient survival. This review consolidates current mechanistic insights into PNI, highlighting immune-neural crosstalk, Schwann cell activation, tumor-nerve feedback loops, and conserved neurotrophic signaling axes. In addition to these shared features, we identify tumor-specific drivers, such as neural progenitor cell involvement in breast cancer, glutamate/NMDA receptor signaling in pancreatic cancer, and epigenetic regulators in gastric and head and neck cancers. A key clinical advancement involves integrating artificial intelligence-driven imaging and machine learning tools for enhanced detection, classification, and prognostic assessment of PNI. These technologies provide scalable, reproducible alternatives to traditional histopathology and underscore the need for standardized diagnostic protocols. By synthesizing molecular, cellular, and computational findings, this review outlines a strategic framework for identifying actionable targets within the nerve-tumor interface. Ultimately, understanding the complex biology of PNI is critical for developing targeted therapies and precision oncology strategies that may reduce recurrence and improve outcomes for patients with high-risk, nerve-invasive tumors.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"283"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the therapeutic potential of FDA-approved ifosfamide and 5-fluorouracil through rational chemical modifications for endometrial cancer treatment.","authors":"Laiba Tanveer, Salma Batool, Hira Mubeen, Izzah Shahid","doi":"10.1007/s12032-025-02821-2","DOIUrl":"10.1007/s12032-025-02821-2","url":null,"abstract":"<p><p>Endometrial or uterine cancers predominantly occur in postmenopausal women, thereby establishing a strong correlation with advanced age. The chemotherapeutic agents ifosfamide and 5-fluorouracil have demonstrated notable efficacy against endometrial cancer by inhibiting cell division and proliferation. Nevertheless, current pharmacological treatments encounter challenges related to drug resistance and adverse effects. To assess the potential of drug modifications, in silico methodologies were employed to alter the molecular structures of ifosfamide and 5-fluorouracil with the aim of enhancing their efficacy and binding affinity to type 1 endometrial cancer. The three-dimensional configurations of mutated KRAS proteins were sourced from the Protein Data Bank. The molecular structures of ifosfamide and 5-fluorouracil were obtained from PubChem and EMBL-EBI, and subsequently modified using Chemsketch. The modifications included the addition of a methyl group, benzene ring, nitrogen atom, cyclopentane ring, and fluorine atoms to the drugs. The binding affinities of these modified drugs to the proteins were visualized using AutoDock Vina. The modified drugs exhibited improved binding affinities of -7.4 and -7.5 kcal/mol with both mutated target proteins. SwissADME analysis and Molinspiration's evaluation of Lipinski's rule parameters suggested that these modified drugs hold promise for the treatment of type 1 endometrial cancer, pending preclinical and clinical trials. This study represents a significant advancement in drug modification as a potential chemotherapeutic strategy for endometrial cancer. Among the two modified drugs, altered 5-fluorouracil demonstrated superior binding affinity and pharmacokinetic properties, rendering it a promising candidate.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"281"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484982","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":"lnc-MTRNR2L12-3 derived from hypoxic breast cancer cell exosomes facilitates angiogenesis via the Src/FAK signaling pathway.","authors":"Li Zheng, Juanfen Mo, Xuesong He, Qi Xu, Yi Bao, Jiayuan Wu","doi":"10.1007/s12032-025-02836-9","DOIUrl":"https://doi.org/10.1007/s12032-025-02836-9","url":null,"abstract":"<p><p>Exosomal long non-coding RNAs (lncRNAs) play crucial roles in breast cancer progression. However, the mechanisms by which hypoxia-induced exosomes mediate angiogenesis through lncRNAs in the tumor microenvironment remain largely unexplored. In this study, exosomes were isolated and characterized from MDA-MB-231 breast cancer cells under normoxic and hypoxic conditions. Hypoxia-induced exosomes (Hyp-exo) were shown to significantly promote angiogenesis. Microarray analysis revealed that lnc-MTRNR2L12-3 was highly enriched in Hyp-exo compared to normoxic exosomes (NC-exo). Functional studies, both in vitro and in vivo, demonstrated that exosomal lnc-MTRNR2L12-3 derived from hypoxic breast cancer cells substantially enhanced angiogenesis. Mechanistically, PCR array and western blot analysis confirmed that silencing lnc-MTRNR2L12-3 inhibited Src/FAK signaling pathway activation in HUVECs, while hypoxia-induced exosomes effectively rescued this suppression. Overall, hypoxia-induced breast cancer exosomes deliver lnc-MTRNR2L12-3 to endothelial cells, promoting angiogenesis through the Src/FAK signaling pathway. These findings provide new insights into targeting angiogenesis in the tumor microenvironment for breast cancer therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"280"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}