Exploration of targeted anti-tumor therapy最新文献

{"title":"Differential molecular mechanisms of bortezomib sensitization to rhTRAIL in non-small cell lung cancer cell lines.","authors":"Paweł Kochany, Janet H Stegehuis, Leonie H A M de Wilt, Gerrit Jansen, Steven de Jong, Godefridus J Peters, Frank A E Kruyt","doi":"10.37349/etat.2025.1002342","DOIUrl":"10.37349/etat.2025.1002342","url":null,"abstract":"<p><strong>Aim: </strong>TNF-related apoptosis-inducing ligand (TRAIL) is a promising targeted anti-cancer agent for several types of cancer, including non-small cell lung cancer (NSCLC). The proteasome inhibitor bortezomib can further potentiate rhTRAIL-induced apoptosis in NSCLC cells. Here, the mechanisms underlying this sensitization were examined in TRAIL-sensitive H460 and TRAIL-resistant A549 and SW1573 NSCLC cells.</p><p><strong>Methods: </strong>NSCLC cell lines were treated with rhTRAIL and bortezomib, and apoptosis was assessed through caspase activation assays, western blotting, and gene silencing of key apoptotic regulators, including Bid, XIAP, and cFLIP. Clonogenic assays were performed to evaluate long-term tumor growth suppression.</p><p><strong>Results: </strong>Bortezomib sensitization mechanisms varied across NSCLC cell lines. Combined rhTRAIL/bortezomib treatment enhanced apoptosis across all cell lines. In TRAIL-sensitive H460 cells, rapid caspase activation was observed, with both extrinsic and intrinsic apoptotic pathways contributing to cell death. Sensitization in H460 cells was predominantly mediated via the caspase-8/Bid amplification loop. In A549 cells, the bortezomib sensitizing effect also relied on the caspase-8/Bid amplification loop. Additionally, the inhibition of Bid and XIAP emphasized the critical role of mitochondrial pathways in apoptosis. In SW1573 cells, limited caspase cleavage was detected, with distinct cleavage patterns suggesting cell-specific apoptotic mechanisms. In this cell line, bortezomib primarily enhanced the extrinsic apoptotic pathway, with XIAP depression further increasing apoptosis. Silencing cFLIP, a caspase-8 inhibitor, significantly improved rhTRAIL sensitivity, emphasizing the critical role of caspase-8 activation in overcoming resistance in SW1573. The clonogenic assay demonstrated that bortezomib combined with rhTRAIL significantly suppressed tumor growth, especially in resistant cell lines.</p><p><strong>Conclusions: </strong>This study underscores bortezomib's ability to differentially enhance rhTRAIL-induced apoptosis by targeting multiple apoptotic regulators. The variety of effects that bortezomib can exert to enhance rhTRAIL-induced apoptosis makes it a very powerful combination for the treatment of NSCLC and various other types of cancer cells.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002342"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12576343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433087","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":"Retraction: Anti-angiogenic effects of <i>Moringa oleifera</i> silver nanoparticles on endothelial cells: in vitro and ex vivo studies.","authors":"","doi":"10.37349/etat.2025.1002343","DOIUrl":"https://doi.org/10.37349/etat.2025.1002343","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.37349/etat.2025.1002332.].</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002343"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12576342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433013","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":"New approaches of green silver nanoparticles for cancer and biomedical applications: a review.","authors":"Puja Kumari, Khushi Quadri, Renu Kadian, Saloni Mishra, Aafrin Waziri, Kaustub Jumle, Kumar Sambhav Verma, Md Sabir Alam","doi":"10.37349/etat.2025.1002341","DOIUrl":"10.37349/etat.2025.1002341","url":null,"abstract":"<p><p>The green synthesis of silver nanoparticles (AgNPs) has recently gained prominence as a sustainable and eco-friendly alternative to conventional physical and chemical methods. Utilizing biological entities such as plant extracts, bacteria, fungi, and biomolecules, the method acts by both reducing and stabilizing mechanisms. It does not use any harmful chemical substances, thus proving to be eco-friendly. Green-synthesized AgNPs exhibit enhanced biocompatibility, stability, and targeted delivery of the drug due to the use of naturally derived surface capping agents. These unique characteristics allow selective interference with cancer cells. The mechanism involved is the generation of reactive oxygen species (ROS), the induction of apoptosis, DNA damage, and cell cycle arrest. Green AgNPs also possess broad-spectrum antimicrobial, catalytic, antiparasitic, and anti-inflammatory properties, supporting the fact that they can be utilised in biomedical fields such as drug delivery, bioimaging, biosensing, tissue engineering, and regenerative medicine. Recent advancements have focused on controlling NP size, shape, and surface functionality to maximize efficacy while simultaneously minimizing cytotoxicity. This review provides a comprehensive analysis of the latest green synthesis strategies, their characterizations, and the molecular mechanisms by which they exert anticancer effects. Recent patents highlight the clinical potential of AgNPs in cancer therapy. US Patent 12201650 (2025) describes green synthesis using <i>Caralluma sinaica</i>, while other patents (WO2007001453, US7462753) outline adaptable biomedical formulations. Studies on biogenic AgNPs also show significant tumor inhibition and selective cytotoxicity against cancer cells. Furthermore, the article discusses current biomedical applications and critically evaluates the limitations, such as reproducibility, toxicity concerns, and scalability for clinical translation. Addressing these challenges is essential for the integration of green AgNPs into mainstream cancer therapeutics. The convergence of nanotechnology and biologically derived synthesis opens promising avenues for the development of safe, effective, and environmentally sustainable medical innovations.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002341"},"PeriodicalIF":0.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12550369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380057","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":"Synergistic anticancer efficacy of optimized curcumin-piperine loaded magnetic nanoparticles for the treatment of colorectal cancer.","authors":"Ritika Puri, Vimal Arora","doi":"10.37349/etat.2025.1002340","DOIUrl":"10.37349/etat.2025.1002340","url":null,"abstract":"<p><strong>Aim: </strong>The current study uses the depicted approach to synthesize curcumin-piperine loaded Poloxamer F-68 coated magnetic nanoparticles (CUR-PIP-F68-Fe₃O₄ NPs) to achieve a synergistic anti-cancer impact on an in vitro HCT-116 colon cancer cell. Integrating magnetic nanoparticle technology with phytoconstituents enhances the potential for targeted drug delivery with minimal systemic toxicity and facilitates therapeutic outcomes.</p><p><strong>Methods: </strong>A Box-Behnken design was employed to optimize the CUR-PIP-F68-Fe₃O₄ NPs prepared by the co-precipitation method. Optimized formulation was evaluated for morphological characteristics, elemental composition, and magnetic properties. An in vitro cytotoxicity assay was conducted to observe the % viability of cells and to further calculate the IC50. Cellular uptake studies were investigated using confocal microscopy.</p><p><strong>Results: </strong>Results showed that the optimised nanoparticles possessed a particle size of 158.7 ± 0.057 nm, zeta potential of -30.3 ± 0.1 mV, and encapsulation efficiency of 98.85 ± 0.066%. Analysis by vibrational sample magnetometer revealed that magnetic saturation was 75.6 emu/g and 50.7 emu/g for bare Fe₃O₄ nanoparticles and drug-loaded magnetic nanoparticles, respectively. Scanning electron microscopy (SEM) depicted the morphological characteristics; elemental composition of synthesized magnetic nanoparticles was confirmed by energy dispersive X-ray (EDX) analysis by illustrating the presence of C (13.50 ± 0.30%), Fe (78.81 ± 1.23%), and O (7.69 ± 0.29%). The MTT assay and cellular uptake studies unveiled that CUR-PIP-loaded magnetic nanoparticles possess a synergistic cytotoxic effect and the highest drug uptake against the HCT-116 colon cell line.</p><p><strong>Conclusions: </strong>The combination approach of curcumin-piperine magnetic nanoparticles to HCT-116 cells enhanced the anticancer efficacy of the curcumin and further demonstrated the potential of this approach to conduct in vivo studies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002340"},"PeriodicalIF":0.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12550504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380064","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":"Engineered nanocarriers for targeted lung cancer therapy: mechanistic innovations and recent clinical progress.","authors":"Heayyean Lee, Khadijah Sajid, Jeehoo Lee","doi":"10.37349/etat.2025.1002339","DOIUrl":"10.37349/etat.2025.1002339","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer mortality worldwide, with progress limited by tumor heterogeneity, drug resistance, and conventional therapy limitations. Nanotechnology-enabled drug delivery offers a transformative approach, enabling the precise engineering of nanocarriers for selective targeting, controlled release, and reduced toxicity. Recent innovations include inhalable systems that achieve localized pulmonary deposition, stimuli-responsive nanocarriers that release drugs in response to tumor microenvironment cues, and nano-immunotherapies that synergize with immune checkpoint blockade. Exosome-based vesicles further offer biomimetic advantages of low immunogenicity and natural tissue tropism. In parallel, theranostic platforms integrate treatment with imaging to enable real-time monitoring of drug delivery and tumor response. This review synthesizes mechanistic advances and translational developments in lung cancer nanomedicine, with emphasis on strategies that overcome biological barriers such as hypoxia, extracellular matrix density, and efflux pump activity. Clinical progress between 2020 and 2025 highlights next-generation antibody-drug conjugates, nanoparticle vaccines, and gene-loaded systems, several of which have reached regulatory approval or advanced trial stages. Together, these advances highlight the potential of nanocarriers to transform lung cancer therapy into more precise, personalized, and less toxic interventions.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002339"},"PeriodicalIF":0.0,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330700","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 cancer vaccines: targeting cryptic and non-canonical antigens for precision immunotherapy.","authors":"Anu Shibi Anilkumar, Sheena Mariam Thomas, Ramakrishnan Veerabathiran","doi":"10.37349/etat.2025.1002338","DOIUrl":"10.37349/etat.2025.1002338","url":null,"abstract":"<p><p>Cancer immunotherapy has revolutionized oncology by harnessing the immune system to target tumor cells. Cancer vaccines that trigger immune responses specific to tumors are becoming more and more popular among new approaches. Nevertheless, traditional tumour-associated antigens are susceptible to immune tolerance and frequently show low immunogenicity. The revolutionary potential of cryptic and non-canonical antigens as new targets for precision immunotherapy is examined in this review. Due to their enhanced tumor selectivity and ability to evade central tolerance, these unconventional antigens present encouraging options for vaccine development. This review examines the mechanisms underlying their antigen production, advanced technologies for their discovery, and various vaccine platforms, highlighting their potential to drive the next generation of cancer vaccines.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002338"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187770","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":"Metabolic plasticity drives specific mechanisms of chemotherapy and targeted therapy resistance in metastatic colorectal cancer.","authors":"Mariam Rojas, Malena Manzi, Sergio Madurga, Fernando Enrique García Velásquez, Maira Alejandra Romero, Silvia Marín, Marta Cascante, Joan Maurel","doi":"10.37349/etat.2025.1002337","DOIUrl":"10.37349/etat.2025.1002337","url":null,"abstract":"<p><p>Microsatellite-stable metastatic colorectal cancer (MSS mCRC) is currently treated with chemotherapy and targeted agents based on RAS and BRAF mutational status. Although these therapies offer initial benefit, most patients rapidly develop resistance, with fewer than 20% remaining progression-free at two years. This review aims to synthesize emerging evidence on the metabolic mechanisms driving treatment resistance in MSS mCRC, with a particular focus on the immune-metabolic signature (IMMETCOLS) classification. We conducted a comprehensive review of preclinical models, transcriptomic datasets, and clinical trial results addressing metabolic adaptations to chemotherapy and targeted therapies in MSS mCRC. The IMMETCOLS framework defines three metabolic subtypes-IMC1, IMC2, and IMC3-each associated with distinct resistance mechanisms. IMC1 exhibits glycolysis and transforming growth factor-β (TGF-β)-dependent signaling enriched in inflammatory fibroblasts, conferring resistance to chemotherapy. IMC2 relies on oxidative phosphorylation and glutamine metabolism, supporting antioxidant defenses and resistance to both cytotoxic agents and anti-EGFR therapies. IMC3 demonstrates lactate-fueled respiration and pentose phosphate pathway activation, contributing to redox balance, DNA repair, and resistance to targeted therapies such as anti-BRAF or KRAS inhibitors. All subtypes display metabolic plasticity under therapeutic pressure. Emerging clinical data support tailoring targeted therapy combinations based on IMMETCOLS subtype, particularly in BRAF- and HER2-positive populations. Understanding subtype-specific metabolic rewiring in MSS mCRC offers novel opportunities to overcome drug resistance. Targeting the metabolic vulnerabilities defined by the IMMETCOLS signature may improve response durability and inform precision treatment strategies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002337"},"PeriodicalIF":0.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187800","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":"Predictive value of 8-hydroxy-2'-deoxyguanosine and 8-nitroguanine production in radiation-induced skin damage after postoperative breast cancer radiotherapy.","authors":"Emmanouil K Verigos, Sofia Sagredou, Kosmas E Verigos, Kyriakos Orfanakos, Constantinos E Alifieris, Maria V Deligiorgi, Panagiotis Dalezis, Mihalis I Panayiotidis, Petros N Karamanakos, Dimitrios T Trafalis","doi":"10.37349/etat.2025.1002336","DOIUrl":"10.37349/etat.2025.1002336","url":null,"abstract":"<p><strong>Aim: </strong>During radiation treatment, reactive oxygen species (ROS) and nitrogen species (RNS) are produced and, by extension, DNA adducts known as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NG), respectively. However, one of the most common side effects induced by radiotherapy is skin toxicity, which affects patients' quality of life. In the present study, we aimed to investigate the potential predictive value of 8-OHdG and 8-NG by exploring the correlations between the alterations in the concentration levels of the two lesions and radiation-induced tissue injury upon exposure to external beam radiotherapy.</p><p><strong>Methods: </strong>For the purpose of this work, we collected blood serum samples from 33 breast cancer patients who received adjuvant radiotherapy. To conduct statistical analysis, we used: (1) linear adjustment to correlate the percent changes of 8-OHdG and 8-NG with the degree of toxicity; and (2) polynomial adaptation and exponential fitting to correlate the percent changes of 8-OHdG and 8-NG with the correlation coefficient <i>r</i> for the development of radiation dermatitis, respectively.</p><p><strong>Results: </strong>According to our findings, there is a statistically significant correlation between the alterations in the 8-OHdG and 8-NG levels and skin grade toxicity across time and varying radiation doses (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Both DNA lesions seem to possess a promising predictive role in radiation dermatitis, while the severity and exact grade of radiation-induced skin toxicity can be determined.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002336"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187802","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":"Genetic and epigenetic landscape of O⁶-methylguanine-DNA methyltransferase (MGMT): implications for DNA repair and cancer therapeutics.","authors":"Shishir Singh, Rajeev Nema, Monisha Banerjee, Atar Singh Kushwah","doi":"10.37349/etat.2025.1002335","DOIUrl":"10.37349/etat.2025.1002335","url":null,"abstract":"<p><p>O⁶-Methylguanine-DNA methyltransferase (MGMT) acts as a genomic custodian, reversing alkylation damage to preserve DNA integrity. However, when its regulatory balance tips via promoter methylation, polymorphisms, or epigenetic silencing, MGMT can become a liability, fuelling cancer progression, treatment resistance, and poor outcomes across malignancies. This review uncovers the nuanced control of MGMT, revealing how its genetic and epigenetic shifts shape tumor behavior, therapeutic response, and risk stratification. We aim to transform molecular insights into actionable clinical strategies, reimagining MGMT as both a biomarker and therapeutic lever. We curated high-impact studies (up to 2025) from PubMed, Scopus, and Web of Science, focusing on MGMT modulation, synthetic lethality, CRISPR-based restoration, and epigenetic therapies. Emerging multi-omics and translational frameworks were prioritized. MGMT's activity is choreographed by an intricate interplay of promoter methylation, histone marks, transcriptional regulation, and microRNA influence. These dynamics critically affect sensitivity to alkylating agents like temozolomide. Intriguingly, MGMT also engages with the immune landscape modulating response to immunotherapies. Innovations in multi-omics, single-cell analytics, and AI-based biomarker profiling are unveiling previously hidden regulatory layers. Decoding MGMT's regulation unlocks new therapeutic frontiers. Cutting-edge strategies from CRISPR to liquid biopsy promise more personalized, resistance-proof cancer care.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002335"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980971","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":"Inflammatory signatures across four photon radiotherapy and proton radiotherapy: mechanisms, mitigation, and quality of life impact.","authors":"Yuting Sheng, Daniel M Han, Mark R Wakefield, Yujiang Fang","doi":"10.37349/etat.2025.1002334","DOIUrl":"10.37349/etat.2025.1002334","url":null,"abstract":"<p><p>Cancer is the second leading cause of death globally and in the United States, second only to cardiovascular disease. Unlike many cardiovascular conditions, cancer is often less preventable, manageable, and curable-even with ongoing technological advancements in medicine. The adverse effects of cancer treatments on cancer patients remain profound due to shared cellular characteristics between cancerous and normal cells; one of the primary adverse effects is treatment-induced inflammation. These inflammatory responses aim to eliminate cancerous cells but often damage normal tissues. Notably, inflammatory side effects vary considerably across the growing diversity of therapeutic approaches. This study reviewed studies between 2007 and 2024, comparing the inflammatory profiles associated with five major radiation therapies (RTs): Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), Image-Guided Radiation Therapy (IGRT), Stereotactic Body Radiation Therapy (SBRT), and Proton Beam Therapy (PBT)-each characterized by distinct mechanistic and therapeutic features. In addition to each radiation modality eliciting distinct inflammatory responses, tissue-specific variability further complicates clinical outcomes. Accordingly, this review also undertakes a cross-tissue comparison of radiation-induced inflammation, with a focus on the gastrointestinal (GI) system, central nervous system (CNS), and skin. However, the variation in treatment modalities and organ-specific inflammatory biomarkers greatly hinders direct comparison across studies. Finally, this review highlights potential inflammatory mitigations, including ambroxol, that may be employed synergistically with RTs, minimizing side effects and enhancing patient outcomes. Taken together, while all modalities offer therapeutic value alongside certain limitations, proton-based therapy demonstrates the greatest potential for minimizing toxicity though its broader adoption remains limited by cost-effectiveness concerns.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002334"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981020","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}