Exploration of targeted anti-tumor therapy最新文献

{"title":"CHD4 and NOX4 expression in thyroid tumor tissues.","authors":"Salma Fenniche, Mohamed Oukabli, Yassire Oubaddou, Allaoui Mohamed, Mohamed Reda Elochi, Abir Alghuzlan, Abdelilah Laraqui, Nadia Dakka, Youssef Bakri, Corinne Dupuy, Rabii Ameziane El Hassani","doi":"10.37349/etat.2026.1002363","DOIUrl":"10.37349/etat.2026.1002363","url":null,"abstract":"<p><strong>Aim: </strong>Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core NURD remodeling complex ATPase that plays a crucial role as a gene repressor. Its overexpression has been reported in several cancers. In papillary thyroid carcinomas (PTCs), CHD4 is overexpressed and associated with aggressive features of the tumor, such as proliferation, migration, and epithelial-mesenchymal transition (EMT). We previously showed in PTCs that NADPH oxidase NOX4 expression is positively regulated by <i>BRAF^V600E</i> mutation, which is the most aggressive alteration in PTCs. In this retrospective study, we wondered whether there is a link between CHD4 and NOX4 protein expression in malignant thyroid tissues.</p><p><strong>Methods: </strong>We explored CHD4 protein expression by immunostaining analysis in 86 human thyroid tissues: 44 thyroid tumor tissues [28 classical forms of PTCs (C-PTCs), 13 follicular variants of PTCs (F-PTCs), and three anaplastic thyroid carcinomas (ATCs)] and 42 of their normal adjacent tissues (NATs). The detection of <i>BRAF^V600E</i> mutation was performed using Sanger sequencing and digital droplet PCR. Statistical analyses were conducted using GraphPad Prism 8 software. Various tests were used to assess the statistical relevance of different correlations, such as the chi-square test, Fisher's exact test, and the Pearson correlation coefficient. A <i>p</i>-value of less than 0.05 indicates statistical significance.</p><p><strong>Results: </strong>The CHD4 protein expression analysis with already published data from our group (<i>BRAF^V600E</i> status and NOX4 expression) reveals a highly significant level of CHD4 protein expression in C-PTCs compared to F-PTCs and ATC. Importantly, 70% of C-PTCs-<i>BRAF^V600E</i> overexpress CHD4 at the protein level, confirming the positive correlation between the CHD4 expression and <i>BRAF^V600E</i> mutation. Furthermore, a high level of CHD4 is associated with the presence of capsular breach and vascular emboli, affirming the involvement of CHD4 in thyroid tumor aggressiveness. Interestingly, we showed for the first time, to our knowledge, a positive correlation between CHD4 and NOX4 protein expression in malignant thyroid tissues.</p><p><strong>Conclusions: </strong>The results of this study suggest that CHD4 could be used as a complementary molecular marker to improve the diagnosis and the management of PTCs-<i>BRAF^V600E</i> .</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002363"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival prediction in triple-negative breast cancer: a Cox model with fairness assessment using ISO/IEC TR 24027:2021 in a MENA cohort.","authors":"Mehrshad Alirezaei Farahani, Fateme Sadeghipour, Hamid Reza Marateb, Maryam Soltan, Azar Naimi, Marjan Mansourian","doi":"10.37349/etat.2026.1002362","DOIUrl":"10.37349/etat.2026.1002362","url":null,"abstract":"<p><strong>Aim: </strong>Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options and poor survival outcomes. Prognostic models developed in Western cohorts rarely assess algorithmic fairness. This study aimed to develop and internally validate a clinically interpretable Cox survival model for TNBC using baseline diagnostic variables and to evaluate its fairness according to ISO/IEC TR 24027:2021 guidelines in a Middle East and North Africa (MENA) cohort.</p><p><strong>Methods: </strong>A total of 138 TNBC patients were included after merging two institutional datasets and removing variables with > 25% missingness. Baseline features comprised age, tumor size, lymph node involvement, tumor grade, Ki-67, type of surgery, metastasis at diagnosis, chemotherapy, and radiotherapy. A Cox proportional hazards (CoxPH) model with six clinically established predictors was fitted to reduce overfitting. Model performance was assessed through five-fold stratified cross-validation using Harrell's concordance index (C-index), receiver operating characteristic area under the curve (AUROC), and calibration curves. Fairness was evaluated using demographic parity, equality of opportunity, predictive equality, and equalized odds metrics following ISO/IEC TR 24027:2021.</p><p><strong>Results: </strong>During follow-up, 34 patients (24.6%) died. Metastasis at diagnosis, high tumor grade, and radical mastectomy were significantly associated with mortality. The CoxPH model achieved a C-index of 0.80 [SE = 0.04; 95% confidence interval (CI): 0.72-0.87] and an AUROC of 0.81 (95% CI: 0.72-0.90). Calibration plots showed strong agreement between predicted and observed survival probabilities, with a modest overall bias of -8.8%. Fairness assessment revealed small but notable disparities in false-positive rates across age groups and surgical categories, while lymph node status and other variables showed no significant bias.</p><p><strong>Conclusions: </strong>This study presents a robust and fairness-aware survival prediction model for TNBC using routinely available clinical features. The model demonstrates strong discrimination, good calibration, and quantifiable fairness across patient subgroups, offering a clinically interpretable and ethically aligned tool to support TNBC risk stratification and decision-making in the MENA region.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002362"},"PeriodicalIF":0.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of haemostatic proteins as markers of disease progression and prognosis in breast cancer.","authors":"Ogochukwu O Izuegbuna","doi":"10.37349/etat.2026.1002361","DOIUrl":"10.37349/etat.2026.1002361","url":null,"abstract":"<p><p>Breast cancer is a leading cause of cancer death in women worldwide. One of the major causes of death from breast cancer is metastatic disease, which results from the malignant cells invading and migrating through blood vessels to distant sites. Several studies have shown that metastasis is facilitated by haemostatic proteins. Breast cancer is characterized by a haemostatic imbalance, which is tilted more to a procoagulant state with resultant thrombotic complications. These elements that are involved in thrombosis also play key roles in different aspects of breast cancer growth, including cancer proliferation and progression, cancer survival, angiogenesis, and metastasis. Some of these elements include platelets, endothelial cells, coagulation factors, and fibrinolytic proteins. There is a close relationship between cancer and many of the haemostatic elements. They are usually increased in metastatic breast cancer and have found use as predictive and prognostic markers. Some have been validated in breast cancer. Due to their seemingly active roles in breast cancer progression, some of the haemostatic proteins are being developed as diagnostic tools in the management of breast cancer. They are equally seen as potential targets for the development of novel therapies in breast cancer or repurposing drugs in current use for the same gain. This review highlights the role haemostatic proteins play in breast cancer progression, and their diagnostic and therapeutic relevance.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002361"},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of weekly docetaxel regimens in prostate cancer: a systematic review and frequentist network meta-analysis.","authors":"Shree Rath, Fatima Sajjad, Khawaja Abdul Rehman, Zaryab Bacha, Ahmad Omar Saleh, Umair Hayat, Umama Alam, Waseef Ullah, Fareeda Brohi, Osama Ahmad, Muzamil Khan, Amar Lal","doi":"10.37349/etat.2026.1002360","DOIUrl":"10.37349/etat.2026.1002360","url":null,"abstract":"<p><strong>Background: </strong>Docetaxel is a cornerstone chemotherapy for metastatic hormone-sensitive and castration-resistant prostate cancer. Although the standard triweekly regimen is widely used, weekly and biweekly schedules are often employed to improve tolerability, particularly in elderly or frail patients. The comparative efficacy and safety of these dosing strategies remain unclear. This study aimed to systematically compare weekly, biweekly, and triweekly docetaxel regimens using a network meta-analysis.</p><p><strong>Methods: </strong>MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to February 2025. Randomized controlled trials and observational retrospective studies comparing weekly, biweekly, and triweekly docetaxel regimens were included. Outcomes assessed were prostate-specific antigen (PSA) response rate, time to treatment failure or progression, and adverse events. A frequentist random-effects network meta-analysis was conducted using R software.</p><p><strong>Results: </strong>Eleven studies involving 1,238 patients were included. PSA response rates did not differ significantly among regimens; triweekly docetaxel showed a numerically lower response compared with weekly dosing (RR = 0.79, 95% CI 0.52-1.22; <i>I²</i> = 41.1%). Time to treatment failure was significantly longer with triweekly dosing compared with weekly dosing (mean difference = 10.91 months, 95% CI 6.94-14.87; <i>I²</i> = 96.8%). Biweekly and triweekly regimens were associated with significantly higher hepatotoxicity compared with weekly dosing (RR = 3.71 and RR = 3.21, respectively; <i>I²</i> = 0%). Vomiting was more frequent with triweekly docetaxel (RR = 2.47, 95% CI 1.31-4.63). No significant differences were observed for overall adverse events, hematologic toxicity, neuropathy, fatigue, febrile neutropenia, nausea, anorexia, or diarrhea.</p><p><strong>Discussion: </strong>Docetaxel dosing schedules show comparable PSA response rates. Triweekly dosing prolongs time to treatment failure but is associated with greater toxicity, whereas weekly dosing offers better tolerability. Treatment decisions should balance efficacy and safety based on individual patient characteristics.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002360"},"PeriodicalIF":0.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12950338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benign, persistent, and invasive: mechanistic and translational approaches to middle‑ear cholesteatoma.","authors":"Pinelopi Samara, Michail Athanasopoulos, Ioannis Athanasopoulos","doi":"10.37349/etat.2026.1002359","DOIUrl":"10.37349/etat.2026.1002359","url":null,"abstract":"<p><p>Acquired middle-ear cholesteatoma is a histologically benign keratinizing squamous epithelial lesion that paradoxically exhibits locally destructive, recurrent, and invasive behavior, often resulting in ossicular erosion, hearing loss, labyrinthine fistula, and, rarely, intracranial complications. Surgical excision remains the primary management strategy; however, recurrence is common due to persistent microenvironmental drivers. Recent mechanistic studies-including single-cell transcriptomics, spatial proteomics, and epigenetic profiling-reveal a multifactorial pathogenesis orchestrated by chronic inflammation, proteolytic extracellular-matrix remodeling, osteoclast activation via RANKL and activin A, epithelial plasticity with partial epithelial-to-mesenchymal transition (EMT), and a dysbiotic, biofilm-forming microbiome. Emerging evidence further implicates oxidative stress, RNA and epigenetic modifications, miRNA dysregulation, and immune cell infiltration as central modulators of lesion chronicity and bone resorption. Collectively, these processes establish a self-sustaining pro-osteolytic microenvironment that drives bone erosion and postoperative recurrence. Cholesteatoma recapitulates several features of malignant lesions-hyperproliferation, local invasion, and stromal/immune cell recruitment-yet remains fundamentally benign, lacking metastatic potential and genomic instability. Its aggression is ecological rather than genetic, highlighting the potential for microenvironment-directed, precision-based strategies. Adjunctive approaches may include local delivery of modulatory agents, targeted interference with inflammatory, proteolytic, osteoclastogenic, and microbial axes, and biomarker-guided patient stratification. Preclinical and early-phase experimental studies assessing target engagement, radiologic stabilization, and molecular surrogates of efficacy could inform safer, mechanism-driven interventions that complement surgery, reduce recurrence, and preserve hearing. Integrating molecular pathobiology with clinical strategy positions cholesteatoma as a model for benign yet locally aggressive, microenvironment-driven disease, providing a roadmap for translational therapies with direct relevance to surgical practice.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002359"},"PeriodicalIF":0.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioblastoma pathophysiology: roles of aging driven changes in STAT3 interactions with NF-κB dimer components in the modulation of the mitochondrial melatonergic pathway and night-time inflammation resolution.","authors":"George Anderson","doi":"10.37349/etat.2026.1002358","DOIUrl":"10.37349/etat.2026.1002358","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a complex condition with a poorly understood pathophysiology and no effective treatment to date. The present article highlights the role of canonical and non-canonical signal transducer and activator of transcription 3 (STAT3) interactions with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the modulation of the mitochondrial melatonergic pathway in GBM microenvironment pathophysiology. The capacity of STAT3 and NF-κB to interact to upregulate the mitochondrial melatonergic pathway is suppressed systemically over the course of aging, thereby attenuating the capacity to achieve inflammation resolution. The suppressed capacity to induce the mitochondrial melatonergic pathway systemically is partly driven by the dramatic 10-fold decrease in pineal melatonin over aging. The attenuation of pineal melatonin in the first half of sleep over aging and aging-accelerating conditions disinhibits the effects of cortisol in the second half of sleep. This decrease in the melatonin/cortisol ratio alters the nature of night-time dampening and resetting in preparation for the coming day by altering cellular and intercellular homeostatic interactions. Aging and aging-accelerating conditions, by impacting the night-time melatonin/cortisol ratio, also suppress the capacity of the vagal nerve to resolve inflammation. This further contributes to systemic changes that influence GBM pathoetiology and ongoing pathophysiology. Aging-associated changes in night-time dampening and resetting provide a novel framework on which many previously disparate bodies of data on GBM pathophysiology can be collated. This has numerous future research, prevention, and treatment implications.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002358"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of explainable artificial intelligence integrating with electronic health record in oncology.","authors":"Yuhan Yang, Xici Liu","doi":"10.37349/etat.2026.1002357","DOIUrl":"10.37349/etat.2026.1002357","url":null,"abstract":"<p><p>Machine learning (ML) and deep learning (DL) models applied to electronic health records (EHRs) have substantial potential to improve oncology care across diagnosis, prognosis, treatment selection, and trial recruitment. However, opacity of many high-performing models limits clinician trust, regulatory acceptance, and safe deployment. Explainable artificial intelligence (XAI) methods aim to make model behavior understandable and actionable in clinical contexts. The present perspective summarizes current XAI approaches applied to EHR-based oncology tasks, identifies key challenges in evaluation, reproducibility, clinical utility, and equity, and proposes pragmatic recommendations and research directions to accelerate safe adoption in oncology. Common XAI categories used with EHR data include feature importance/interaction methods, intrinsically interpretable models, attention mechanisms, dimensionality reduction, and knowledge distillation or rule extraction. Tree-based models with SHapley Additive exPlanations (SHAP) explanations dominate recent EHR studies. Other interpretable strategies, such as generalized additive models and rule sets, appear in settings where transparency is prioritized. Gaps include inconsistent reporting, scarce formal evaluation of explanations for clinical utility, limited reproducibility for data and code availability, inadequate external validation, and insufficient consideration of fairness and equity that these issues are particularly important in oncology, where heterogeneity and stakes are high. Overall, integrating XAI with EHR-driven oncology models is promising but underdeveloped, which requires further progress by multi-stakeholder evaluation frameworks, reproducible pipelines, prospective and multicenter validations, and equity-aware design. The field should prioritize clinically meaningful explanations beyond ranking features and study how explanations affect clinician decision-making and patient outcomes.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002357"},"PeriodicalIF":0.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical need for robust decision support in the era of precision cancer therapeutics.","authors":"Maurie Markman","doi":"10.37349/etat.2026.1002356","DOIUrl":"10.37349/etat.2026.1002356","url":null,"abstract":"","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002356"},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation nanocarriers for precision antitumor therapy: from passive targeting to intelligent response.","authors":"Dilpreet Singh, Akshay Kumar","doi":"10.37349/etat.2025.1002355","DOIUrl":"10.37349/etat.2025.1002355","url":null,"abstract":"<p><p>The evolution of nanocarrier-based drug delivery systems has transformed the paradigm of cancer therapeutics, advancing from conventional cytotoxic formulations to intelligent, adaptive nanosystems capable of precision targeting. Early-generation nanocarriers exploited the enhanced permeability and retention (EPR) effect for passive tumor accumulation, yet their therapeutic efficiency remained constrained by tumor heterogeneity, limited penetration, and off-target toxicity. Emerging nanotechnologies now integrate active targeting, stimuli-responsive components, and biomimetic strategies to achieve spatiotemporal control over drug release and tumor-selective action. These \"intelligent\" nanocarriers are designed to recognize molecular signatures, respond dynamically to tumor microenvironmental cues such as pH, redox gradients, hypoxia, and enzymatic activity, and even engage in real-time feedback through imaging or biosensing modules. In addition, hybrid and multifunctional platforms-combining liposomes, micelles, dendrimers, polymeric nanoparticles, and inorganic systems-offer programmable functionality and synergistic delivery of chemotherapeutic, gene-editing, and immunomodulatory agents. This review delineates the mechanistic basis of passive and active targeting, highlights recent innovations in stimuli-responsive and biomimetic nanocarriers, and explores translational and regulatory perspectives shaping their clinical journey. By integrating nanotechnology with systems biology and artificial intelligence, next-generation nanocarriers promise to redefine the landscape of precision antitumor therapy.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002355"},"PeriodicalIF":0.0,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12753623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic properties of plant-derived prebiotics in melanoma.","authors":"Emily Kay, Mahnaz Kazi, Jeremy Burton, Seema Nair Parvathy","doi":"10.37349/etat.2025.1002354","DOIUrl":"10.37349/etat.2025.1002354","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI) therapy has revolutionized metastatic melanoma treatment, yet only a subset of patients respond effectively, and the treatment can induce a variety of immune-related adverse events (irAEs), including colitis. The gut microbiome plays a critical role in determining patient responses to immunotherapy, prompting exploration of gut-modifying strategies such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) to overcome both primary and acquired resistance and improve treatment outcomes. Prebiotics, defined as dietary substrates that selectively support the growth and/or activity of beneficial gut microorganisms, represent a feasible and safe strategy for microbiome reshaping. Plant-derived prebiotics like castalagin, inulin, fructooligosaccharides, galactooligosaccharides, mushroom extract, kale extract, and konjac glucomannan offer unique advantages over synthetic or animal-derived alternatives due to their natural fiber content alongside their ability to enhance gut microbial diversity. Prebiotics are known to achieve health benefits by selectively stimulating beneficial gut bacteria, producing short-chain fatty acids (SCFAs) that modulate the host immune system, suppressing pathogenic microbes, enhancing mucin production, and modulating systemic and gut-associated immune responses. SCFAs generated through prebiotic fermentation influence host innate and adaptive immunity and regulate metabolic activity via inhibition of histone deacetylases (HDACs), influencing mTOR/MAPK signaling and cytokine production. They also act as ligands for G-protein-coupled receptors (GPCRs), altering intracellular calcium and cAMP to modulate immune cell gene expression. However, the specific mechanisms by which individual prebiotics interact with host genetics, beneficial gut bacteria, and their metabolites are not very well understood. This is crucial to optimize their therapeutic potential in cancer immunotherapy. This review synthesizes current evidence on plant-derived prebiotics, highlighting the impact of beneficial gut bacteria and their metabolites. Given their established safety for human consumption, prebiotics represent a promising, low-risk option to improve gut microbiome composition and potentially enhance immunotherapy and clinical outcomes in cancer.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002354"},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}