OncoTargets and therapy最新文献

{"title":"High-Dose Twice-Daily Thoracic Radiotherapy for Limited-Stage Small-Cell Lung Cancer: A Real-World Retrospective Experience from Two Tertiary Centers.","authors":"Oded Icht, Bilal Krayim, Mor Moskovitz, Daniel Reinhorn, Ofer Rotem, Itamar Averbuch, Nir Peled, Aaron M Allen","doi":"10.2147/OTT.S576505","DOIUrl":"https://doi.org/10.2147/OTT.S576505","url":null,"abstract":"<p><strong>Background: </strong>Hyperfractionated thoracic radiotherapy (RT) is a standard component of curative treatment for limited-stage small-cell lung cancer (LS-SCLC). While 45 Gy in 30 twice-daily fractions remains the most validated regimen, recent Phase II data suggest that dose-escalated RT using 60 Gy in 40 fractions may improve outcomes. However, real-world data on this intensified regimen remain scarce.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of LS-SCLC patients treated with 60 Gy in 40 twice-daily fractions and concurrent platinum-etoposide chemotherapy at two tertiary centers. Modern radiation techniques were employed. Key outcomes included overall survival (OS), progression-free survival (PFS), patterns of failure, and treatment-related toxicity.</p><p><strong>Results: </strong>Thirteen patients were included in the analysis. The median age at diagnosis was 59 years; 61.5% were female. At a median follow-up of 15 months, the 2-year OS rate was 71.4%, and the median OS was 30.9 months. The overall response rate was 60%. Most failures were distant; only one local failure was observed. Acute grade ≥3 esophagitis occurred in 7.6%, and no patients experienced grade ≥2 pneumonitis. Hematologic toxicity, particularly neutropenia, was frequent but manageable. No treatment-related deaths occurred.</p><p><strong>Conclusion: </strong>In this cohort, delivery of dose-escalated twice-daily thoracic radiotherapy using contemporary techniques was feasible and associated with acceptable toxicity in routine clinical practice. Survival outcomes were comparable to those reported in phase II studies of this approach. These findings warrant confirmation in larger, multi-institutional, or registry-based studies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"576505"},"PeriodicalIF":2.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623371","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":"Enhancing Immunotherapy in Diffuse Large B-Cell Lymphoma: The Synergistic Potential of Metabolic Checkpoint Inhibitors and Immunomodulation.","authors":"Meghana K Rajendraprasad, John C Riches","doi":"10.2147/OTT.S581821","DOIUrl":"https://doi.org/10.2147/OTT.S581821","url":null,"abstract":"<p><p>For many patients with diffuse large B-cell lymphoma (DLBCL), frontline chemoimmunotherapy is curative; nonetheless, up to 40% of patients develop relapse or refractory disease. Immunotherapeutic approaches, such as immunomodulatory drugs, bispecific antibodies and chimeric antigen receptor T-cell therapy, have improved outcomes for relapsed/refractory DLBCL over the past ten years. However, treatment failure is still frequent because of tumor antigen loss, T-cell dysfunction, and an immunosuppressive tumor microenvironment (TME). DLBCL is a highly metabolically active cancer that impairs efficient anti-tumor immune responses by depleting vital nutrients and producing immunosuppressive metabolites such lactate, adenosine, and kynurenine. Targeting metabolic checkpoints, such as glutamine metabolism, indoleamine 2,3-dioxygenase, adenosine signaling, and lactate transport, may remodel the TME and improve the effectiveness of immunotherapy, according to new research. The immune metabolic interaction that restricts long-lasting responses is the main topic of this study, which summarizes current immunotherapeutic strategies in DLBCL. To improve T-cell fitness and overcome immunotherapy resistance, we critically assessed the preclinical and early clinical data supporting metabolic checkpoint inhibition. We also emphasize translational issues and potential future paths for logical combination treatments. Importantly, this review distinguishes itself from existing literature by specifically focusing on the integration of metabolic checkpoint inhibition with established immunotherapies in DLBCL, an area that remains underexplored. While preclinical data are promising, clinical evidence for many metabolic checkpoint inhibitors in DLBCL remains limited, and further prospective clinical studies are required to validate their therapeutic potential.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"581821"},"PeriodicalIF":2.8,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623381","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 Strategy for Treating Elderly Patients with Advanced Non-Small Cell Lung Cancer: Exploring the Efficacy and Safety of Anlotinib Combined with PD-1/PD-L1 Inhibitors.","authors":"Chuanzhen Chi, Li Li, Chunhua Xu","doi":"10.2147/OTT.S578933","DOIUrl":"https://doi.org/10.2147/OTT.S578933","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore whether the combination of anlotinib and immunotherapy is an effective and safe alternative to chemotherapy for clinical treatment. Provide a new treatment plan for elderly patients who are unwilling to undergo chemotherapy, intolerant to chemotherapy, or have poor ECOG PS scores.</p><p><strong>Methods: </strong>This is a single-center retrospective investigation that collected clinical data of 58 elderly aNSCLC patients treated with anlotinib monotherapy or anlotinib plus PD-1/PD-L1 inhibitor combination therapy at Nanjing Chest Hospital during the period from January 1, 2020 to December 31, 2023, with the study being subject to a limited sample size.</p><p><strong>Results: </strong>Fifty-eight elderly patients were evaluated after two cycles of anlotinib monotherapy and combined therapy. In the monotherapy group of 28 patients, the ORR and DCR were 25.0% (7/28) and 78.6% (22/28), respectively. Besides, the mPFS and the mOS reached up to 5.4 months (95% CI, 4.4-6.4 months) and 11.2 months (95% CI, 7.2-15.2 months), respectively. In the group with combination therapy of 30cases, the ORR for this group was calculated at 30.0% (9/30), the DCR was higher, at 86.7% (26/30), the mPFS and the mOS were determined to be 8.5 months (95% CI, 7.3-9.7 months) and 17.8 months (95% CI, 13.2-22.4 months), respectively. In multivariate COX analysis, brain metastasis and treatment methods were found to be independent risk factors for PFS alongside OS. Both groups had a comparable overall incidence of adverse events (AEs), at 70.0% and 64.3% respectively, with no statistically significant difference noted in the rate of grade 3 and above adverse events (23.3% versus 17.9%).</p><p><strong>Conclusion: </strong>Anlotinib combined with immunotherapy demonstrated superior efficacy and better tolerability than anlotinib alone. The combination of anlotinib and immunotherapy may provide a \"chemo-free\" treatment mode for elderly patients with non-small cell lung cancer who refuse or cannot tolerate chemotherapy and have poor ECOG PS scores.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"578933"},"PeriodicalIF":2.8,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623457","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":"HMGB1 as Double-Edged Regulator of Cancer Therapy: Mechanistic Roles in Chemotherapy Resistance and Immunotherapy Response.","authors":"Haoyuan Li, Bao Wen, Shuguang Bao, Yanqing Gao, Xinze Liu, Subudao Bao, Ao Li, Qiang Guo, Bateer Han","doi":"10.2147/OTT.S581730","DOIUrl":"https://doi.org/10.2147/OTT.S581730","url":null,"abstract":"<p><p>High-mobility group box 1 (HMGB1) is a ubiquitous non-histone nuclear protein with multifaceted roles in cancer biology. Emerging evidence suggests that the biological effects of HMGB1 are highly context-dependent, being determined by its subcellular localization, redox state, and release kinetics. Nuclear HMGB1 regulates chromatin structure and genome stability, whereas cytoplasmic HMGB1 controls autophagy and cell survival. When released extracellularly during cellular stress or therapy-induced immunogenic cell death, HMGB1 functions as a damage-associated molecular pattern that activates innate and adaptive immunity through pattern-recognition receptors such as Toll-like receptor 4. In this narrative review, we synthesize recent mechanistic and translational studies to clarify how HMGB1 regulates tumor proliferation, metastasis, and therapeutic responses under different treatment modalities. We particularly discuss the dual roles of HMGB1 in chemotherapy and emerging immunotherapies. Collectively, these insights highlight HMGB1 as a potential biomarker of treatment response and a therapeutically modifiable node for optimizing chemo-immunotherapy combination strategies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"581730"},"PeriodicalIF":2.8,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13037637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593453","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":"Close-to-Patient Models for Gastric Cancer: From Patient-Derived Xenograft Towards a Novel Gastric Cancer Mini-Tumor Model.","authors":"Sarah K Hakuno, Joëlle Zonneveld, Stefanus G T Janson, Anthea Van der Wielen, Eleonore B Kuhlemaijer, Maud Steenbakkers, Leonie Plug, Eveline De Jonge-Muller, Eduard P De Winter, Margreet R De Vries, Tom Van Wezel, Stijn Crobach, Lukas J A C Hawinkels, Andrea Vallés-Martí, Marije Slingerland","doi":"10.2147/OTT.S586407","DOIUrl":"10.2147/OTT.S586407","url":null,"abstract":"<p><strong>Purpose: </strong>Gastric cancer (GC) is the fifth most lethal form of cancer. Because of its late diagnosis, high intratumor heterogeneity, and the presence of a dense stromal compartment, GC is less susceptible to systemic treatments compared to other tumor types. Many systemic therapies, developed to support curative and palliative treatment for GC and other cancers, did not reach the clinic, which might be due to the fact that preclinical data, obtained from simple cell-based models, does not translate to the complex GC tumor structure and the occurrence of drug resistance. Therefore, this study is aimed to establish fibroblast-rich, close-to-patient models for GC and evaluate their robustness by comparison with the primary GC tissue from the respective patients.</p><p><strong>Material and methods: </strong>Five different GC models were established: I) a subcutaneous and II) orthotopic patient-derived xenograft (PDX) model, III) an in vitro patient-derived organoid (PDO) model, which was IV) subcutaneously engrafted in vivo, and V) co-cultured with GC fibroblasts to form a novel multicellular fibroblast-rich GC model. Histology, immunohistochemistry, mutational status and tumor/stroma composition were compared between the parental tissues and the various models.</p><p><strong>Results: </strong>Both PDX models reflected the histological structure of the parental tissue, consisting of distinct parenchymal and stromal compartments. Primary tumor mutations were maintained in the PDX, as well as markers of clinical interest, like HER2. Orthotopic GC-PDX models showed high growth rates, accompanied by significant stromal accumulation. GC-PDOs showed histological similarities with parental tissues, maintaining the various histological phenotypes. Engrafted subcutaneously in mice, these organoids generated stroma-rich tumors. To mimic these features in vitro, we established a multicellular model composed of GC-associated fibroblasts and GC organoids, aggregating into complex multicellular structures with high similarity to parental GC tumor tissues.</p><p><strong>Conclusion: </strong>We generated five close-to-patient GC models, which can potentially facilitate preclinical evaluations of novel therapies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"586407"},"PeriodicalIF":2.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581760","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":"Long-Term Survival in an Elderly HCV Patient with Double Primary Malignant Tumors Managed with Local Therapy Only.","authors":"Bing-Yu Yang, Yi Zhou, Jian-Zhou Li, Nan Yang, Xiao-Jing Liu","doi":"10.2147/OTT.S582880","DOIUrl":"10.2147/OTT.S582880","url":null,"abstract":"<p><p>Hepatitis C virus (HCV) infection is associated with both hepatic and extrahepatic malignancies. We report a 95-year-old male with chronic HCV infection who developed recurrent hepatocellular carcinoma (HCC) and subsequent splenic diffuse large B-cell lymphoma (DLBCL), achieving a 13-year survival. This patient was managed exclusively with local therapies, receiving multiple rounds of radiofrequency ablation (RFA) for five episodes of HCC recurrence and undergoing splenectomy for the primary splenic DLBCL, entirely avoiding systemic chemotherapy. Despite his advanced age and dual primary malignancies, he has maintained normal liver function and shows no evidence of lymphoma progression at the latest follow-up. This case underscores the potential of a patient-centric treatment approach, highlighting that in select very elderly or high-risk patients, aggressive systemic therapy may not be necessary to achieve long-term survival and high quality of life. The successful outcome challenges conventional management paradigms and contributes to the growing evidence supporting minimally invasive, localized interventions for complex oncological scenarios in geriatric populations. It emphasizes the importance of individualized risk-benefit assessment and tumor biology in guiding treatment decisions, offering a new perspective on optimizing outcomes for patients where standard aggressive therapies are contraindicated.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"582880"},"PeriodicalIF":2.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581768","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":"PLK1 as A Potential Prognostic Marker of Gastric Cancer Through MEK-ERK Pathway on PDTX Models [Retraction].","authors":"","doi":"10.2147/OTT.S611151","DOIUrl":"10.2147/OTT.S611151","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S169880.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"611151"},"PeriodicalIF":2.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581718","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":"Glycosylation-Related Gene Signature Identifies MFNG as a Key Driver of Proliferation and Metastasis in Colorectal Cancer.","authors":"Xinji Gao, Qiang Li, Qingshui Wang, Jun Wang, Lan Zhao, Ting Yan, Xiang Yu","doi":"10.2147/OTT.S572377","DOIUrl":"10.2147/OTT.S572377","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) ranks as the third most common malignancy and second leading cause of cancer-related mortality worldwide. Aberrant glycosylation has emerged as a hallmark of cancer, yet systematic analyses of glycosylation-related gene expression patterns and their prognostic implications in CRC remain limited.</p><p><strong>Methods: </strong>We conducted comprehensive analyses of 214 glycosylation-related genes using TCGA and GEO datasets. Differential expression analysis identified significantly altered genes, followed by LASSO Cox regression to construct a four-gene glycosylation-Related Gene Signature (GRGS). We validated the model across multiple independent cohorts and performed functional experiments with MFNG knockdown in CRC cell lines and zebrafish xenograft models.</p><p><strong>Results: </strong>We identified 54 differentially expressed glycosylation-related genes in CRC tissues. The four-gene signature comprising MFNG (manic fringe), UST (uronyl 2-sulfotransferase), SLC35D1 (solute carrier family 35 member D1), and GALNT7 (polypeptide N-acetylgalactosaminyltransferase 7) demonstrated robust prognostic performance across validation cohorts. GRGS-High patients exhibited significantly shorter overall survival and were associated with advanced tumor stages. MFNG emerged as the top predictor, with high expression correlating with poor survival. Functional validation confirmed that MFNG knockdown significantly inhibited CRC cell proliferation, migration, and invasion both in vitro and in vivo.</p><p><strong>Conclusion: </strong>Our study establishes GRGS as a reliable prognostic tool for CRC risk stratification and identifies MFNG as a promising therapeutic target. These findings provide valuable insights into glycosylation-mediated CRC progression and offer potential clinical applications for precision oncology.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"572377"},"PeriodicalIF":2.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574459","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 Review of SIK2 in Ovarian Cancer: Function and Emerging Targeted Therapies.","authors":"Zhengyang Xu, Xiangting Gao","doi":"10.2147/OTT.S583883","DOIUrl":"10.2147/OTT.S583883","url":null,"abstract":"<p><p>Ovarian cancer, a common gynecologic malignancy, is associated with a poor prognosis owing to difficulties in early detection, high recurrence rates, and frequent therapy resistance. Salt-inducible kinase 2 (SIK2), a serine/threonine kinase frequently overexpressed in ovarian cancer, has emerged as a potential key driver of tumor progression. It is implicated in diverse processes, including metabolic reprogramming, cell proliferation, DNA damage repair, metastasis, and chemoresistance. Consequently, SIK2 is increasingly recognized as a promising target for developing novel therapeutic strategies. Unlike previous reviews that broadly cover the SIK family or general ovarian cancer metabolism, this review provides a SIK2-centered perspective, comprehensively synthesizing its multifaceted oncogenic roles and systematically evaluating emerging targeted therapies-including ATP-competitive inhibitors (ARN-3261, MRIA9), a protein degrader (SIC-19), and a novel hydrogel delivery system (Gel Nap-S+HG). Despite these promising developments, it is important to note that most SIK2-targeted agents are still in preclinical stages, and several critical hurdles remain to be addressed before clinical translation-including off-target toxicity, limited selectivity, and the lack of validated predictive biomarkers for patient stratification. By integrating current mechanistic insights with an up-to-date evaluation of emerging therapies, this review provides a foundational framework for guiding future research and supporting the clinical development of SIK2-targeted strategies in ovarian cancer.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"583883"},"PeriodicalIF":2.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574980","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":"Aloperine Induces Ferroptosis of Colorectal Cancer Cells via the Nrf2 Pathway.","authors":"Jun An, Lixuan Tian, Runze Wang, Demiao Ma, Jingxuan Song, Ruihan Yuan, Jingru Wu, Yuxuan Bu, Jianping Wang","doi":"10.2147/OTT.S575500","DOIUrl":"10.2147/OTT.S575500","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the effects of ALO on apoptosis and ferroptosis in colorectal cancer HCT116 and SW480 cells and the underlying mechanisms.</p><p><strong>Methods: </strong>Cells were treated with varying ALO concentrations. CCK-8 assay assessed proliferation. Flow cytometry detected apoptosis. Lipid peroxidation was measured by BODIPY 581/591 C11 dye oxidation and TBA method. GSH content was determined by DTNB method. ROS and intracellular iron levels were assessed using fluorescent probes and iron assays. Molecular docking analyzed ALO-Nrf2 binding. Immunofluorescence detected Nrf2 expression. Western blot quantified apoptosis-related proteins (Bax, Bcl-2) and ferroptosis-related proteins (Nrf2, GPX4, xCT, DMT1). Effects of Nrf2 overexpression on ALO-treated cells were observed.</p><p><strong>Results: </strong>ALO inhibited cell viability and increased apoptosis dose-dependently. It elevated lipid peroxidation and intracellular iron while reducing GSH. Ferroptosis inhibitors DFO and Fer-1 reversed cell death and reduced apoptosis. ALO induced ROS production, upregulated Bax/Caspase3, and downregulated Bcl-2. Molecular docking suggested ALO binds to Nrf2 via hydrogen bonding. Immunofluorescence and Western blot showed ALO suppressed Nrf2, GPX4, xCT, and DMT1 expression concentration-dependently. Nrf2 overexpression significantly attenuated ALO's inhibitory effects on proliferation and its induction of ferroptosis and apoptosis.</p><p><strong>Conclusion: </strong>ALO suppresses colorectal cancer cell proliferation by inducing apoptosis and ferroptosis via inhibition of the Nrf2 signaling pathway.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"19 ","pages":"575500"},"PeriodicalIF":2.8,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521538","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}