{"title":"Nanoparticle-Driven Radiotherapy for Pancreatic Cancer: Pioneering Precision Biotherapy for Enhanced Efficacy and Reduced Toxicity.","authors":"Wen-Yi Zhang","doi":"10.1089/cbr.2025.0088","DOIUrl":"10.1089/cbr.2025.0088","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Pancreatic cancer remains one of the most challenging malignancies to treat, characterized by limited therapeutic options and persistently poor survival rates. Conventional radiotherapy presents several limitations, including nonspecific tumor targeting, elevated toxicity to adjacent healthy tissues, and intrinsic radioresistant pancreatic tumors, necessitating innovative treatment strategies. In comparison to previous studies, which reported a median survival rate of 12 months for patients undergoing conventional radiotherapy, the results of this study demonstrate a significant improvement, with a median survival increase to 18 months using a novel targeted approach. Additionally, our findings show a 30% reduction in off-target tissue toxicity, compared with the 45% toxicity seen with traditional methods. <b><i>Methods:</i></b> Nanoparticle-enhanced radiotherapy (NERT) introduces a novel therapeutic approach using biocompatible nanoparticles functionalized with tumor-specific ligands. These nanoparticles serve as radiosensitizers, selectively increasing the local radiation dose within the tumor microenvironment while minimizing exposure normal tissues. This targeted delivery mechanism leverages precision nanotechnology to enhance the therapeutic index. <b><i>Results:</i></b> Preclinical studies have shown NERT significantly improves treatment outcomes in pancreatic cancer. The method achieves 97.4% increase in treatment efficiency, 45.2% reduction in toxicity, 96.3% enhancement in patient outcomes, 40.3% decrease in systemic side-effects, and 98.6% improvement in tumor targeting when compared with conventional radiotherapy. <b><i>Conclusions:</i></b> These findings underscore the transformative potential of NERT in addressing key limitations of traditional pancreatic cancer treatments. By integrating precision targeting with advanced nanotechnology, NERT enhances the efficacy radiotherapy while mitigating adverse effects, thereby improving patient outcomes. This innovative modality holds promise for redefining clinical protocols and elevating standards of care in oncology. The proposed method achieves the treatment efficiency by 97.4%, toxicity by 45.2%, patient outcome by 96.3%, systematic side-effect by 40.3%, and tumor targeting by 98.6%.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"450-457"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxidative Stress Links Thyroid Autoimmunity to Cancer: Peroxiredoxin 2 Protection via Genomic and Single-Cell Insights.","authors":"Jie Kang, Shengcai Wang, Xin Ni","doi":"10.1177/10849785251360744","DOIUrl":"10.1177/10849785251360744","url":null,"abstract":"<p><p><b><i>Objective:</i></b> This study identifies shared genetic factors linking Hashimoto's thyroiditis (HT) and thyroid cancer (TC) using an integrated multiomics approach. <b><i>Methods:</i></b> We combined Mendelian randomization (MR) analysis using FinnGen genome-wide association study data, single-cell RNA sequencing of 76,243 thyroid cells, and machine learning classification models to identify causal genes and their expression patterns across disease states. <b><i>Results:</i></b> MR analysis identified 10 genes with consistent directional effects across both diseases. Peroxiredoxin 2 (PRDX2) emerged as the strongest protective factor (HT: odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.31-0.94; TC: OR = 0.68, 95% CI: 0.50-0.91). Single-cell analysis revealed progressively decreased PRDX2 expression from normal thyroid to papillary to anaplastic TC. Machine learning confirmed PRDX2 as the most discriminative gene for disease classification. PRDX2 expression negatively correlated with inflammatory TNF-TNFRSF1A signaling and was associated with improved survival in patients with TC (hazard ratios = 0.33, 95% CI: 0.11-0.96, <i>p</i> = 0.043). <b><i>Conclusions:</i></b> <i>PRDX2</i> functions as a key protective factor in both HT and TC pathogenesis, likely through modulation of oxidative stress and inflammatory signaling. These findings provide mechanistic insights into the HT-TC relationship and highlight <i>PRDX2</i> as a promising therapeutic target for thyroid diseases.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"470-480"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hua Xu, Yi Huang, Feng Li, Na Liu, Yuhong Wang, Min Qiu, Weiqi Nian
{"title":"Investigation on the Inhibitory Mechanism of Chai Hu Hua Ji Tang on Liver Cancer Based on a Network Pharmacology Analysis.","authors":"Hua Xu, Yi Huang, Feng Li, Na Liu, Yuhong Wang, Min Qiu, Weiqi Nian","doi":"10.1177/10849785251372756","DOIUrl":"https://doi.org/10.1177/10849785251372756","url":null,"abstract":"<p><p><b><i>Context:</i></b> Hepatocellular carcinoma (HCC) poses a serious threat to human health due to its high incidence and mortality rates. In recent years, the application of traditional Chinese medicine (TCM) in the comprehensive treatment of liver cancer has gained increasing attention. Clinical practices have demonstrated the mighty efficacy of Chai Hu Hua Ji Tang (CHHJT) in liver cancer treatment, yet its underlying mechanism remains unexplored. <b><i>Objective:</i></b> This article reveals the underlying of CHHJT in the context of hepatic malignancies. <b><i>Materials and Methods:</i></b> CHHJT and HCC-related targets were screened through network pharmacology. PLC/PRF/5 and MHCC97L cells were treated with CHHJT as the experimental group, and those without CHHJT as the control group. After 24 and 48 h, IC<sub>50</sub>, cloning, scratch, invasion, and Western blot/quantitative real-time PCR were assayed. Subsequently, a model of orthotopic liver cancer was developed in BALB/c nude mice. A volume of 0.2 mL of PBS served as the control group, while the experimental group received 0.2 mL of a 3.55 g/mL CHHJT solution. After 4 weeks, the <i>in vivo</i> effect of CHHJT was evaluated. <b><i>Results:</i></b> According to our results of IC<sub>50</sub>, a concentration of 1600 μg/mL was the most effective dosage for CHHJT to suppress growth of HCC cells. Additionally, CHHJT was found to curb cellular proliferation, migration, and invasiveness. Transcription and protein levels of <i>FLT3</i>, <i>PIK3CA</i>, and <i>AKT1</i> targets reduced following CHHJT treatment. In the nude mouse model, CHHJT treatment greatly reduced tumor cell volume, integrated tumor cell structure, markedly reduced nodules, well-grown cells, and substantially increased apoptosis. <b><i>Discussion and Conclusion:</i></b> CHHJT is likely to impede the PI3K/AKT signaling pathway by downregulating FLT3 protein expression, ending up with suppression of HCC cell differentiation and proliferation, as well as their viability. Future research could stratify patients based on their likelihood of responding to PI3K/AKT pathway-targeted therapies. This could aid in patient selection and optimize treatment outcomes.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benchun Yan, Yuqiu Gao, Yulong Zou, Long Zhao, Zhiping Li
{"title":"Proteogenomic Biomarker Profiling for Predicting Radiolabeled Immunotherapy Response in Resistant Prostate Cancer.","authors":"Benchun Yan, Yuqiu Gao, Yulong Zou, Long Zhao, Zhiping Li","doi":"10.1177/10849785251366066","DOIUrl":"https://doi.org/10.1177/10849785251366066","url":null,"abstract":"<p><p>Treatment resistance prevents patients with preoperative chemoradiotherapy or targeted radiolabeled immunotherapy from achieving a good result, which remains a major challenge in the prostate cancer (PCa) area. A novel integrative framework combining a machine learning workflow with proteogenomic profiling was used to identify predictive ultrasound biomarkers and classify patient response to radiolabeled immunotherapy in high-risk PCa patients who are treatment resistant. The deep stacked autoencoder (DSAE) model, combined with Extreme Gradient Boosting, was designed for feature refinement and classification. The Cancer Genome Atlas and an independent radiotherapy-treated cohort have been utilized to collect multiomics data through their respective applications. In addition to genetic mutations (whole-exome sequencing), these data contained proteomic (mass spectrometry) and transcriptomic (RNA sequencing) data. Maintaining biological variety across omics layers while reducing the dimensionality of the data requires the use of the DSAE architecture. Resistance phenotypes show a notable relationship with proteogenomic profiles, including DNA repair pathways (Breast Cancer gene 2 [BRCA2], ataxia-telangiectasia mutated [ATM]), androgen receptor (AR) signaling regulators, and metabolic enzymes (ATP citrate lyase [ACLY], isocitrate dehydrogenase 1 [IDH1]). A specific panel of ultrasound biomarkers has been confirmed in a state deemed preclinical using patient-derived xenografts. To support clinical translation, real-time phenotypic features from ultrasound imaging (e.g., perfusion, stiffness) were also considered, providing complementary insights into the tumor microenvironment and treatment responsiveness. This approach provides an integrated platform that offers a clinically actionable foundation for the development of radiolabeled immunotherapy drugs before surgical operations.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanglong Zhang, Pengcheng Zhang, Huanyu Zhang, Zhuoya Zhang, Juntao Ran
{"title":"Exploring Targeted Delivery Systems for Boron Neutron Capture Therapy and Its Potential as a Promising Therapeutic Modality for Hepatocellular Carcinoma.","authors":"Tanglong Zhang, Pengcheng Zhang, Huanyu Zhang, Zhuoya Zhang, Juntao Ran","doi":"10.1177/10849785251370873","DOIUrl":"https://doi.org/10.1177/10849785251370873","url":null,"abstract":"<p><p><b><i>Background:</i></b> Boron neutron capture therapy (BNCT) is a precision binary radiotherapy. In this modality, thermal neutrons combine with 10B to induce a nuclear reaction that kills tumor cells. Its therapeutic efficacy depends on the targeted accumulation of boron delivery agents. BNCT has demonstrated clinical efficacy in treating head and neck cancers and recurrent gliomas. However, there is limited evidence regarding its application in hepatocellular carcinoma (HCC). This review systematically examines recent advances in novel boron carriers. It also assesses the potential of BNCT for treating HCC and aims to provide a new therapeutic option for HCC. <b><i>Methods:</i></b> We used a systematic research approach to investigate the latest advances in novel boron carrier development. We also analyzed existing clinical data related to BNCT treatment for HCC. We aimed to systematically assess the feasibility and potential of applying BNCT to HCC. <b><i>Results:</i></b> Newly designed boron carriers show significantly enhanced targeted aggregation within tumor cells and reduced systemic toxicity compared to traditional carriers. Preliminary clinical studies have confirmed the potential efficacy of BNCT in inhibiting HCC growth. Notably, BNCT possesses the unique advantage of precise tumor targeting, which shows promising potential in minimizing damage to surrounding normal liver tissue. <b><i>Conclusion:</i></b> The progress made in the development of boron carriers has built a solid foundation for improving the efficacy and safety of BNCT treatment for HCC. By addressing current limitations in boron delivery and clinical evidence, BNCT has the potential to complement existing treatment modalities, improve outcomes for HCC patients, and provide new directions for the clinical treatment of HCC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xianqiao Li, Shukai Wang, Ulf Dietrich Kahlert, Tianchi Zhou, Kexin Xu, Wenjie Shi, Xiaofei Yan
{"title":"Artificial Intelligence-Driven Ultrasound Identifies Rare Triphasic Colon Cancer and Unlocks Candidate Genomic Mechanisms via Ultrasound Genomic Techniques.","authors":"Xianqiao Li, Shukai Wang, Ulf Dietrich Kahlert, Tianchi Zhou, Kexin Xu, Wenjie Shi, Xiaofei Yan","doi":"10.1177/10849785251370718","DOIUrl":"https://doi.org/10.1177/10849785251370718","url":null,"abstract":"<p><p><b><i>Background:</i></b> Colon cancer is a heterogeneous disease, and rare subtypes like triphasic colon cancer are difficult to detect with standard methods. Artificial intelligence (AI)-driven ultrasound combined with genomic analysis offers a promising approach to improve subtype identification and uncover molecular mechanisms. <b><i>Methods:</i></b> The authors used an AI-driven ultrasound model to identify rare triphasic colon cancer, characterized by a mix of epithelial, mesenchymal, and proliferative components. The molecular features were validated using immunohistochemistry, targeting classical epithelial markers, mesenchymal markers, and proliferation indices. Subsequently, ultrasound genomic techniques were applied to map transcriptomic alterations in conventional colon cancer onto ultrasound images. Differentially expressed genes were identified using the <i>edgeR</i> package. Pearson correlation analysis was performed to assess the relationship between imaging features and molecular markers. <b><i>Results:</i></b> The AI-driven ultrasound model successfully identified rare triphasic features in colon cancer. These imaging features showed significant correlation with immunohistochemical expression of epithelial markers, mesenchymal markers, and proliferation index. Moreover, ultrasound genomic techniques revealed that multiple oncogenic transcripts could be spatially mapped to distinct patterns within the ultrasound images of conventional colon cancer and were involved in classical cancer-related pathway. <b><i>Conclusions:</i></b> AI-enhanced ultrasound imaging enables noninvasive identification of rare triphasic colon cancer and reveals functional molecular signatures in general colon cancer. This integrative approach may support future precision diagnostics and image-guided therapies.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting the <i>MCM10/p53/p21/CCND1</i> Axis in Colorectal Cancer: Evaluating the Therapeutic Potential of Ultrasound.","authors":"Hao Wu, Changyu Wen, Zheng Jiang","doi":"10.1177/10849785251364091","DOIUrl":"https://doi.org/10.1177/10849785251364091","url":null,"abstract":"<p><p><b><i>Background:</i></b> Colorectal cancer (CRC), the second leading cause of cancer-related deaths globally, continues to lack effective early diagnostic biomarkers and therapeutic strategies. Minichromosome maintenance protein 10 (<i>MCM10</i>), a replication initiation factor implicated as a pan-cancer marker, remains poorly characterized in CRC. Its role within the <i>p53/p21</i>/Cyclin D1 (<i>CCND1</i>) regulatory axis and its potential as a therapeutic target, particularly under ultrasound-based modulation, warrants investigation. <b><i>Methods:</i></b> Integrated bioinformatic analyses were conducted using public databases to evaluate <i>MCM10</i> expression and clinical significance. Clinical CRC specimens were analyzed via qPCR and immunohistochemistry to validate <i>MCM10</i> expression. Functional assays, including colony formation, cell counting kit-8 (CCK-8), Transwell migration/invasion, and flow cytometry, assessed the biological effects of <i>MCM10</i> knockdown on proliferation, apoptosis, and cell cycle. Western blotting and rescue experiments elucidated signaling pathways. A CRC mouse xenograft model was established to evaluate <i>in vivo</i> tumor growth. The therapeutic modulation of <i>MCM10</i>-related pathways using ultrasound-based interventions was preliminarily assessed. <b><i>Results:</i></b> <i>MCM10</i> expression was significantly upregulated in cell lines and CRC tissues, and correlated with poor prognosis. Silencing <i>MCM10</i>-impaired CRC cell proliferation, invasion, migration, and induced G1/S cell cycle arrest suppressed epithelial-mesenchymal transition and increased apoptosis. Mechanistically, <i>MCM10</i> knockdown activated the <i>p53/p21</i> axis and downregulated <i>CCND1</i> expression. <i>In vivo</i>, <i>MCM10</i> inhibition suppressed xenograft tumor growth. Ultrasound exposure exhibited the potential to enhance the therapeutic effects of <i>MCM10</i> suppression by modulating the <i>MCM10/p53/p21/CCND1</i> axis. <b><i>Conclusions:</i></b> These findings reveal that <i>MCM10</i> promotes CRC malignancy through inhibiting the tumor-suppressive <i>p53/p21/CCND1</i> pathway. Targeting this axis, particularly through ultrasound-enhanced delivery or sensitization strategies, holds promise as a novel therapeutic approach in CRC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sachin Tayal, Satvika Sharma, Jasmine Sati, Swati Bhat, Shreyans Jain, Rakesh Kapoor, Devinder K Dhawan, Vijayta D Chadha
{"title":"Radiosynthesis and <i>In Vitro</i> Bioevaluation of <sup>99m</sup>Tc-Temozolomide as a Radiotracer for Glioma Imaging.","authors":"Sachin Tayal, Satvika Sharma, Jasmine Sati, Swati Bhat, Shreyans Jain, Rakesh Kapoor, Devinder K Dhawan, Vijayta D Chadha","doi":"10.1177/10849785251364113","DOIUrl":"https://doi.org/10.1177/10849785251364113","url":null,"abstract":"<p><p><b><i>Background:</i></b> Temozolomide (TMZ), an alkylating drug used for the treatment of gliomas, has to date not been exploited for its potential role as a radionuclide-imaging probe. Therefore, the present study radiosynthesizes [<sup>99m</sup>Tc]Tc-TMZ and evaluates its specificity for glioma using C6 cell lines. <b><i>Methods:</i></b> TMZ was labeled with <sup>99m</sup>Tc, optimized for reaction conditions and radiochemical purity. Physicochemical characterization was performed by evaluating plasma protein binding, stability in saline and serum, and partition coefficient. Furthermore, the cellular uptake and internalization mechanism of [<sup>99m</sup>Tc]Tc-TMZ were determined in C6 cells. The toxicity of the radiotracer was determined by performing the MTT and hemolysis assays. <b><i>Results:</i></b> The radiocomplex was synthesized with >90% radiochemical purity. The radiocomplex exhibited neutral charge, high lipophilicity, low plasma protein binding, and physiological stability in <i>in vitro</i> conditions. Cell binding studies exhibited [<sup>99m</sup>Tc]Tc-TMZ specificity for C6 cells in a concentration- and time-dependent manner, with maximum uptake at 12.5 μg and passive diffusion as the primary mode of transport. Toxicity studies revealed more than 50% damage to the cells with minimal hemolytic activity at 50 μg concentration of TMZ in radiocomplex. <b><i>Conclusions:</i></b>These preliminary findings suggest the specificity of [<sup>99m</sup>Tc]Tc-TMZ for C6 cells and warrant further exploration as a SPECT radiotracer for glioma imaging.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in STING Pathway Modulation for Cancer and Immunotherapy: A Comprehensive Review of Preclinical and Clinical Studies (2020-2024).","authors":"Rahaman Shaik, Komal Suthar, Chandrika Balija, Shifa Aleem, Fatima Sarwar Syeda, Sana Syeda, Shireen Begum","doi":"10.1177/10849785251362585","DOIUrl":"https://doi.org/10.1177/10849785251362585","url":null,"abstract":"<p><p>In cancer immunotherapy, the stimulator of interferon genes (STING) pathway regulation has become a promising new approach, offering potential solutions to overcome limitations of current treatments. Recent advances have revealed intricate mechanisms of STING activation and regulation, leading to the development of novel small-molecule agonists with improved properties. Preclinical studies have shown that STING agonists can convert \"cold\" tumors to \"hot\" ones, enhancing immune cell infiltration and overcoming resistance to checkpoint inhibitors. Combination strategies, particularly with existing immunotherapies and conventional treatments, have demonstrated synergistic effects. Early clinical trials evaluating STING agonists, both as monotherapies and in combination with checkpoint inhibitors, have yielded promising results. More specific methods have been made possible by biomarker investigations, which have revealed light on mechanisms of action and possible response predictors. Indirect STING activation through ENPP1 inhibition has emerged as a novel strategy, offering more controlled antitumor immunity enhancement while minimizing systemic toxicity. Innovative delivery systems, including nanoparticles and exosome-based therapies, improve STING modulators' therapeutic index. While challenges remain, including precise regulation of STING activation and managing immune-related adverse events, rapid progress suggests that STING-targeted therapies could become cornerstone treatments. By harnessing innate immunity and enhancing its interplay with adaptive responses, STING modulators offer a potentially more accessible, cost-effective, and broadly applicable approach to cancer immunotherapy, addressing many current treatment limitations.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirel Cabrera, Ximena Camacho, Marcos Tassano, Carolina Perroni, Marcelo Fernández, Ana Laura Reyes, Andrea Paolino, Eduardo Savio, Pablo Cabral, Juan Pablo Gambini
{"title":"Theranostic Radiotracers for Melanoma Imaging and Therapy: A Comparative Study of Subcutaneous and Intradermal Tumor Models Using DOTA-Re-CCMSH Peptides.","authors":"Mirel Cabrera, Ximena Camacho, Marcos Tassano, Carolina Perroni, Marcelo Fernández, Ana Laura Reyes, Andrea Paolino, Eduardo Savio, Pablo Cabral, Juan Pablo Gambini","doi":"10.1089/cbr.2025.0023","DOIUrl":"10.1089/cbr.2025.0023","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Melanoma, with its aggressive behavior and high metastatic potential, presents significant clinical challenges. The melanocortin-1 receptor (MC1R) is a promising target for diagnosis and therapy due to its overexpression in metastatic melanoma. <b><i>Methods:</i></b> This study compares the theranostic potential of DOTARe-CCMSH, labeled with <sup>68</sup>Ga and <sup>177</sup>Lu, in subcutaneous and intradermal murine melanoma models over an extended period. Radiolabeling achieved high molar activities for both isotopes, enabling precise imaging and therapeutic applications. <b><i>Results:</i></b> PET imaging with [<sup>68</sup>Ga]Ga-DOTA-Re-CCMSH showed specific tumor accumulation, with a mean uptake of 2.25 ± 0.2% ID/g at 2 hours post-injection, enhanced by gelofusine pre-administration. SPECT imaging with [<sup>177</sup>Lu]LuDOTA-Re-CCMSH revealed significant and sustained tumor uptake in both models, with mean values of 21.9 ± 7.98 for subcutaneous and 19.8 ± 5.36 for intradermal tumors at 4 hours post-injection, extending up to 24 hours. This study tracked the therapeutic radiotracer uptake for up to 7 days post-injection, showing continued retention and tumor specificity, especially in the tumor-to muscle ratio, which reached 172 at 24 hours. <b><i>Discussion and Conclusions:</i></b> Comparative biodistribution analyses highlighted differences between subcutaneous and intradermal models, including distinct peritumoral edema arrangements. These findings emphasize the value of long-term theranostic studies in understanding tumor behavior and the efficacy of radiolabeled peptides in melanoma treatment, advancing personalized oncology approaches.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"398-409"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}