International journal of oncology最新文献

{"title":"The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).","authors":"Yangxi Fu, Zheng Wang, Lin Liu, Xudong Tang","doi":"10.3892/ijo.2026.5925","DOIUrl":"10.3892/ijo.2026.5925","url":null,"abstract":"<p><p>Stearoyl‑CoA desaturase‑1 (SCD1) has emerged as a critical nexus linking lipid metabolic reprogramming to the regulation of cell death. Frequently overexpressed in digestive system malignancies ‑ including gastric, liver and colorectal cancers ‑ SCD1 represents a promising therapeutic target. This review systematically examined how SCD1, through its lipid‑modifying functions, governs three key forms of regulated cell death ‑ ferroptosis, autophagy and apoptosis ‑ thereby driving malignant progression and mediating therapy resistance in digestive cancers. Building on this mechanistic framework, the specific contributions of these regulatory pathways to tumor biology and their association with drug resistance were delineated. Current preclinical therapeutic strategies targeting SCD1 were then highlighted, encompassing both monotherapy and combination approaches with ferroptosis inducers, chemotherapeutic agents or targeted drugs. Finally, key challenges and outline future directions for drug development and clinical translation in this rapidly evolving field were discussed.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 4","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Punicalagin as a multi‑targeted therapeutic agent against endometrial cancer.","authors":"Zeeshan Ahmad Bhutta, Dohee Ahn, Hong Kyu Lee, Kyung-Chul Choi","doi":"10.3892/ijo.2026.5922","DOIUrl":"10.3892/ijo.2026.5922","url":null,"abstract":"<p><p>Endometrial cancer (EC) has become an increasing clinical concern as the incidence is rising, and treatment options available for advanced disease or recurrent disease are limited. In the present study, the anticancer potential of punicalagin (PCG), a natural ellagitannin polyphenol that comes from pomegranate, was characterized using both <i>in vitro</i> and <i>in vivo</i> models in EC. Two EC cell lines (Ishikawa and SNU‑539) treated with increasing doses of PCG showed dose‑dependent inhibition of cell proliferation and demonstrated a decrease in colony formation. PCG inhibited Transwell migration and an increase in E‑cadherin expression, indicating an inhibition of epithelial‑mesenchymal transition. Further experimental work characterized the mechanisms by which PCG acted and revealed that it decreased the mitochondrial membrane potential and subsequently increased levels of reactive oxygen species, which led to apoptosis as shown by increased BAX expression and Hoechst/PI staining. In addition, PCG showed signs of autophagy, especially in the Ishikawa cells, as indicated by increased levels of LC3‑IIB and the formation of autophagic vacuoles. <i>In vivo</i> studies using a xenograft mouse model showed that treatment with PCG significantly reduced tumor volume and weight, whereas body weight was not significantly affected, thus highlighting strong anticancer efficacy coupled with very low toxicity. Overall, the present study highlights PCG as a promising natural compound with multitarget anticancer activity against EC and warrants further preclinical and clinical research as a potential treatment option.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 4","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KIAA1429 knockdown alleviates osteosarcoma  progression by destabilizing SLC7A11 mRNA via m6A methylation to promote ferroptosis.","authors":"Hui Zeng, Yunyan Zhong, Dingbiao Zeng, Shiliang Xiao, Song Zou","doi":"10.3892/ijo.2026.5929","DOIUrl":"10.3892/ijo.2026.5929","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a highly aggressive bone tumor with limited therapeutic options. As a key component of the N6‑methyladenosine (m6A) methyltransferase complex, KIAA1429 contributes to tumor progression; however, its role in OS remains unclear. For the present study, four human OS cell lines (MG63, 143B, U2OS and Saos‑2) and an osteoblast cell line (hFOB1.19) were cultured <i>in vitro</i>, and KIAA1429 was knocked down in 143B and U2OS cells. To evaluate functional effects, cell proliferation was assessed using a Cell Counting Kit‑8 assay, apoptosis was evaluated by flow cytometry, migration was assessed by Transwell assay and invasion was analyzed using a wound healing assay. Subsequently, ferroptosis was induced using erastin, and analyzed by western blotting, ELISA, C11‑BODIPY staining and m6A‑modified RNA immunoprecipitation‑quantitative PCR. In addition, actinomycin D was used to inhibit transcription and to assess mRNA stability. The interaction between KIAA1429 and solute carrier family 7 member 11 (SLC7A11) was validated using a dual‑luciferase reporter assay. Furthermore, a xenograft model was established in BALB/c nude mice to assess tumor growth and ferroptosis markers, and tumor histology and proliferation were examined using hematoxylin and eosin staining and immunohistochemistry. The results revealed that KIAA1429 was significantly upregulated in OS cells, whereas its knockdown markedly suppressed malignant cellular behaviors. Downregulation of KIAA1429 also enhanced erastin‑induced ferroptosis. Mechanistically, KIAA1429 knockdown reduced m6A modification and decreased the stability of SLC7A11 mRNA, leading to its downregulation. Rescue experiments demonstrated that SLC7A11 overexpression reversed the effects of KIAA1429 knockdown on ferroptosis and malignant phenotypes. <i>In vivo</i>, KIAA1429 knockdown inhibited tumor growth and promoted ferroptosis, effects that were reversed by SLC7A11 overexpression. In conclusion, KIAA1429 knockdown may suppress OS progression by inhibiting m6A‑dependent SLC7A11 expression, thereby promoting ferroptosis. Targeting the KIAA1429/SLC7A11 axis may thus represent a promising therapeutic strategy for OS.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 4","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.","authors":"Michal Pastorek, Veronika Simko, Martina Takacova, Monika Barathova, Maria Bartosova, Luba Hunakova, Olga Sedlakova, Sona Hudecova, Olga Krizanova, Franck Dequiedt, Silvia Pastorekova, Jan Sedlak","doi":"10.3892/ijo.2026.5931","DOIUrl":"10.3892/ijo.2026.5931","url":null,"abstract":"<p><p>Following the publication of the above article, an interested reader drew to the Editor's attention that the β‑actin control protein band featured in the right‑hand lane of Fig. 1A on p. 54 appeared to be strikingly similar to the β‑actin control protein band featured in the right‑hand lane of Fig. 2B on the same page, albeit after vertical flipping and with possible horizontal and vertical resizing. Owing to the lack of availability of the raw western blot data due to the time that has elapsed since this paper was published, the authors have repeated the experiments and provided new western blots for these figures, which fully confirm the veracity of the findings presented in the originally published study. The revised versions of Figs. 1 and 2 are shown on the next page. In response to an additional query, the authors also wished to point out that the raw data from the PCR analysis (which were presented to the Editorial Office for inspection) confirmed that the data were correctly assembled from the original electropherograms, and that the part of Fig. 4C associated with the A2780/ADR cells was composed of two parts that came from the same experiment and the same run. They were put together as such, simply because they were loaded in two separate parts of the gel. The authors thank the Editor of <i>International Journal of Oncology</i> for granting them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 47: 51‑60, 2015; DOI: 10.3892/ijo.2015.2987].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 4","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).","authors":"Jinghao Pan, Boyang Li, Ruonan Lin, Chenlu Fang, Lucy Yue Lau, Zehao Hong, Yi Chen","doi":"10.3892/ijo.2026.5932","DOIUrl":"10.3892/ijo.2026.5932","url":null,"abstract":"<p><p>Immune escape and therapeutic resistance remain major obstacles to durable benefit from cancer immunotherapy, yet transcript‑based or abundance‑based biomarkers often fail to capture the regulatory states that determine effective immune control. Post‑translational modifications (PTMs) form a dynamic protein‑state layer that rapidly reshapes protein stability, trafficking, complex assembly, and signaling persistence under tumor‑intrinsic and therapy‑imposed stress. In the present review, a biomarker‑oriented framework is proposed in which PTM biology is interpreted through three recurrent immune constraints: Checkpoint competence, tumor visibility and stress‑conditioned immune‑state programming. Within this framework, programmed death‑ligand 1 is viewed as a protein‑state biomarker problem rather than a static expression marker; tumor visibility is defined by durable antigen‑presentation competence and interferon‑linked reinforcement; and stress‑driven immune dysfunction is interpreted through metabolite‑sensitive PTM rewiring and chromatin‑coupled suppressive stabilization. Rather than cataloguing PTMs comprehensively in cancer immunity, the present review focuses on five core exemplar PTM axes, glycosylation, palmitoylation, ubiquitin editing, phosphorylation and lactylation, because they repeatedly map to rate‑limiting immune constraints, are supported by mechanistic evidence, and represent candidate assay‑compatible or intervention‑relevant state variables at differing levels of translational maturity. It is further outlined how integrated proteogenomic, immuno‑peptidomic, and spatial datasets can be used to discover candidate PTM‑state biomarkers, validate mechanism‑proximal readouts in prespecified pretreatment and on‑treatment settings, and prioritize single or co‑dominant state constraints for patient stratification, pharmacodynamic monitoring, and rational combination design. By organizing PTM biology around measurable state variables rather than modification class alone, the present review provides a phase‑aware translational framework for candidate biomarker discovery, fit‑for‑purpose validation, constraint‑guided stratification, and therapeutic prioritization in cancer immunotherapy.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 4","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of xeroderma pigmentosum group C on the characteristics and regulatory mechanisms of lung cancer stem cells.","authors":"Ben Yang, Yang Yang, Weiyu Wang, Yubing Wang, Huaijie Wang, Liya Qin, Yongming Wang, Sipeng Sun, Shubo Wang, Meihua Qu","doi":"10.3892/ijo.2026.5933","DOIUrl":"10.3892/ijo.2026.5933","url":null,"abstract":"<p><p>Lung cancer is one of the most common and deadly forms of cancer worldwide, with >80% of cases being non‑small cell lung cancer. Its recurrence and drug resistance have been major challenges in clinical treatment, posing a serious threat to the lives of patients. The present study found that high xeroderma pigmentosum group C (XPC) expression markedly reduced the proliferation capacity and stem cell characteristics of the lung cancer cell lines A549‑XPC and H460‑XPC. In addition, XPC overexpression led to a decreased in the proportion of cells in the G₂/M phase proportion, suggesting alterations in the cell cycle process. MTS assays showed that XPC overexpressing cells demonstrated markedly higher sensitivity to chemotherapy drugs compared with control cells. Furthermore, the clonogenic and anchorage‑independent spheroid formation capacities of the cells were markedly inhibited with high XPC expression and the phosphorylation levels of the JAK/STAT pathway and the expression levels of stemness‑associated markers were markedly altered. <i>In vivo</i> studies validated the effect of high XPC expression on tumorigenicity using a subcutaneous tumor model, with tumor volumes of 134.04±46.77 mm³ and 324.64±85.31 mm³ and weights of 164.24±76.16 mg and 434.70±115.72 mg for subcutaneously injected A549‑XPC and A549‑CTR cells, respectively. High expression of XPC in the A549 cells significantly affected tumor volume (P<0.05) and weight (P<0.01) <i>in vivo</i>. The present findings suggested that high XPC expression is associated with reduced proliferation, migration and stem cell‑like properties in lung cancer cells, enhances their sensitivity to chemotherapy drugs and suppresses tumor growth <i>in vivo</i>. These observations supported further investigation of XPC as a potential therapeutic target and prognostic marker for lung cancer, offering new strategies to improve treatment outcomes and prolong patient survival.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 4","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single <i>in situ</i> intratumoral low‑dose shikonin hydrogel plus mild photothermal therapy elicits systemic antitumor immunity in immune‑cold triple‑negative breast cancer.","authors":"Tao Pan, Zujian Feng, Ting Shang, Jun Jiang, Fang Zhang","doi":"10.3892/ijo.2026.5930","DOIUrl":"10.3892/ijo.2026.5930","url":null,"abstract":"<p><p>Shikonin (SHK) possesses potent antitumor activity; however, its severe non‑selective toxicity greatly limits the feasibility of conventional systemic administration for cancer therapy. Likewise, mild photothermal therapy (PTT) has intrinsic limitations, including inadequate induction of immunogenic cell death (ICD) and compensatory activation of immunosuppressive pathways, such as increased IDO1 activity and PD‑L1 expression. In the present study, low‑dose SHK and gold nanorods were co‑encapsulated within a supramolecular hydrogel (mPECT) and administered by intratumoral injection to achieve localized combination therapy with mild PTT. Mild PTT rapidly triggered antitumor immune activation within the immunosuppressive tumor microenvironment, whereas SHK sustained this response by suppressing PTT‑induced IDO1 activation and PD‑L1 upregulation and by markedly enhancing ICD. The mPECT hydrogel enabled prolonged local retention and controlled release of SHK, minimizing rapid systemic exposure while preserving therapeutic efficacy at the tumor site. This localized combination of SHK and mild PTT elicited a robust adaptive antitumor immune response that not only inhibited primary tumor growth but also suppressed the progression of untreated distant tumors and generated durable antitumor immune memory. These findings indicate that a single intratumoral administration of low‑dose SHK‑loaded hydrogel combined with mild PTT can induce potent systemic antitumor immunity, supporting the further development of localized SHK‑based therapeutic strategies for the treatment of immune‑cold tumors.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 4","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples.","authors":"Giovanni Luca Gravina, Andrea Mancini, Guido Ranieri, Boris Di Pasquale, Francesco Marampon, Luigi Di Clemente, Enrico Ricevuto, Claudio Festuccia","doi":"10.3892/ijo.2026.5916","DOIUrl":"10.3892/ijo.2026.5916","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding Figs. 2A and 4B (and possibly also Fig. 4A), certain of the gel lanes within these figure parts (showing numbered cultures) appeared to contain duplicated data (specifically, lanes 2‑4 and 8‑10 in Fig. 2A, lanes 5 and 6 in Fig. 4A, and lanes 1‑4 and 7‑10 in Fig. 4B). Upon performing an independent analysis of the data in this paper, it also came to light that the β‑actin data in Fig. 3A and the Desmin data in Fig. 3E had appeared in a previous paper published in <i>American Journal of Pathology</i> that featured entirely different authors, although comparing the affiliations of the papers, one of the universities was the same. Given the apparent duplications of data within this paper itself and the re‑use of data that had originally appeared in a different article, the Editor of <i>International Journal of Oncology</i> has decided that it should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The corresponding author, Claudio Festuccia, takes full responsibility for the raised concerns and clarifies that the other co-authors were not directly involved in the preparation of the submitted figures. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 42: 2116‑2122, 2013; DOI: 10.3892/ijo.2013.1892].</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoediting and precision biomarkers in prostate cancer: The emerging role of liquid biopsy, immune contexture and HLA genotype (Review).","authors":"Constantin N Baxevanis, Savvas Stokidis, Sotirios P Fortis, Maria Goulielmaki, Ourania E Tsitsilonis, Angelos D Gritzapis","doi":"10.3892/ijo.2026.5917","DOIUrl":"10.3892/ijo.2026.5917","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Prostate cancer (PCa) remains a leading cause of cancer‑related mortality in men despite advances in screening and localized treatment. The clinical heterogeneity of PCa, ranging from indolent disease to aggressive, lethal phenotypes, underscores the urgent need for reliable biomarkers that improve diagnosis, prognostication and therapeutic decision‑making. While prostate‑specific antigen testing has reduced mortality, its limited specificity has resulted in overdiagnosis and overtreatment. The present review provides a comprehensive overview of contemporary and emerging biomarkers that support a precision‑medicine approach to PCa management. The present review summarizes established and novel diagnostic, prognostic and predictive biomarkers, including serum‑ and urine‑based assays, genomic and transcriptomic signatures and multiparametric imaging. Particular emphasis is placed on liquid biopsy technologies (circulating tumor cells, circulating tumor DNA and extracellular vesicles), which offer minimally invasive, real‑time insights into tumor burden, molecular evolution and treatment resistance, although their clinical implementation remains context‑dependent and is currently most established in advanced disease settings rather than routine early‑stage management. The present review discusses the strengths and limitations of these platforms, highlighting disease‑stage dependency, technical variability and sensitivity constraints. Beyond tumor‑intrinsic markers, tissue‑based immune biomarkers that capture the tumor immune microenvironment, including immune cell density, spatial organization, checkpoint expression and immune‑related gene signatures, are explored. Evidence indicates that 'immune‑hot' tumors characterized by CD8&lt;sup&gt;+&lt;/sup&gt; T‑cell infiltration and interferon‑γ signaling are associated with improved outcomes, whereas immunosuppressive macrophage‑ or regulatory T‑cell‑dominant profiles predict poor prognosis. However, these associations are not uniform across studies and PCa remains largely resistant to immunotherapy, underscoring the need to improve the understanding of immune evasion mechanisms and the contextual limitations of immune biomarkers. Furthermore, the present review examines the emerging role of germline human leukocyte antigen class I genotype as a prognostic and predictive biomarker, explicitly integrating it with tissue‑based immune contexture and liquid biopsy readouts by proposing immunoediting as a unifying mechanistic framework that links allele‑specific antigen presentation to immune infiltration. Finally, the present review highlights the prognostic significance of preexisting tumor‑antigen‑specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells, which reflect an active antitumor immune response and predict a favorable progression‑free survival and responsiveness to immunotherapeutic strategies. Collectively, the present review underscores the need for standardized, multimodal biomarker integration and prospective validation to ","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).","authors":"Yanling Xu, Hanmei Duan, Peng Lu, Feng Liu","doi":"10.3892/ijo.2026.5915","DOIUrl":"10.3892/ijo.2026.5915","url":null,"abstract":"<p><p>Non‑small cell lung cancer (NSCLC), as the main type of lung cancer, is characterized by high heterogeneity and a complex tumor microenvironment (TME), which are key factors contributing to therapeutic resistance, recurrence and metastasis. In recent years, the interaction between neural stem cells (NSCs) and NSCLC, known as the 'NSC‑NSCLC axis', has gradually become a research hotspot at the intersection of tumor biology and cancer neuroscience. The present review summarizes the extensive overlap between NSCs and NSCLC stem cells in terms of molecular markers and signaling pathways, and discusses the possible mechanisms through which NSCLC cells 'hijack' NSC programs to enhance stemness, therapeutic resistance and metastatic potential. The present review further discusses how the TME actively recruits NSCs and drives their functional reprogramming, thereby promoting tumor progression through the paracrine secretion of neurotrophic factors, the induction of angiogenesis, remodeling of the immune microenvironment and the formation of synapse‑like connections. In addition, the regulatory networks of neurotransmitters, neurotrophic factors and neuropeptides in NSCLC are reviewed, with particular emphasis on evaluating the potential and challenges of emerging therapies targeting neurotransmitter receptors, perineural invasion, neuroendocrine differentiation and brain metastasis. Unlike previous reviews that focused predominantly on a single mechanism or flux, the present review adopts an integrated perspective of the 'neural stem cell‑non‑small cell lung cancer axis' to link three tiers: Molecular hijacking, microenvironment remodeling and clinical translation. The present review further highlights translational research priorities, including targeting neurotransmitter receptors, perineural invasion, neuroendocrine transformation and brain metastasis. Additionally, it is proposed that single‑cell and spatial omics are poised to advance this field from phenomenological description toward precise subtyping, providing a novel therapeutic strategy for NSCLC shifting from 'tumor eradication' to 'reprogramming the tumor microecology'.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"69 3","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}