Yufeng Du, Mohammad Arian Hassani, Chunhong Li, Zhijia Zhao, Yikun Liu, Chengtao Zhang, Jinsong Yan
Background
Refractory/relapsed acute myeloid leukemia (R/R-AML) typically exhibits resistance to conventional chemotherapy, resulting in a poor overall therapeutic outcome. Salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the primary treatment option in such patients. However, posttransplant relapse is still a challenge, with no established effective regimens.
Case
In this case report, we present the case of a 40-year-old male diagnosed with R/R-AML who underwent salvage allo-HSCT. Unfortunately, after 4 months of follow-up, a relapse occurred. We modified the immunosuppressive therapy and administered donor lymphocyte infusion (DLI) and decitabine but failed to obtain complete remission (CR). Subsequently, a combination of venetoclax (Ven) and azacitidine (Aza), followed by the DLI regimen, was initiated. The patient achieved CR with no measurable residual disease.
Conclusion
Our data suggest that the administration of Ven in combination with Aza followed by the DLI regimen used for early post-HSCT relapsed AML could serve as a valuable reference for treating similar patients.
{"title":"Venetoclax-Based Therapy for Early Relapse in Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Minireview","authors":"Yufeng Du, Mohammad Arian Hassani, Chunhong Li, Zhijia Zhao, Yikun Liu, Chengtao Zhang, Jinsong Yan","doi":"10.1002/cnr2.70450","DOIUrl":"10.1002/cnr2.70450","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Refractory/relapsed acute myeloid leukemia (R/R-AML) typically exhibits resistance to conventional chemotherapy, resulting in a poor overall therapeutic outcome. Salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the primary treatment option in such patients. However, posttransplant relapse is still a challenge, with no established effective regimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>In this case report, we present the case of a 40-year-old male diagnosed with R/R-AML who underwent salvage allo-HSCT. Unfortunately, after 4 months of follow-up, a relapse occurred. We modified the immunosuppressive therapy and administered donor lymphocyte infusion (DLI) and decitabine but failed to obtain complete remission (CR). Subsequently, a combination of venetoclax (Ven) and azacitidine (Aza), followed by the DLI regimen, was initiated. The patient achieved CR with no measurable residual disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data suggest that the administration of Ven in combination with Aza followed by the DLI regimen used for early post-HSCT relapsed AML could serve as a valuable reference for treating similar patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12747801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145853887","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}
RAN binding protein 3-like (RANBP3L), a member of the Ran-binding protein family, has been linked to various cellular functions, but the role in cancer remains underexplored. In this research, we assessed the diagnostic and prognostic value of RANBP3L in pan-cancer, especially in liver hepatocellular carcinoma (LIHC).
Aims
This study aimed to explore the pan-cancer expression, prognostic value, and immune-related roles of RANBP3L, especially emphasis on validating its diagnostic and prognostic significance in hepatocellular carcinoma.
Methods
We analyzed RANBP3L expression of 33 cancer types from TCGA data and assessed its relationship with overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). We used TIMER2.0 and CIBERSORT to explore the correlation between RANBP3L expression and immune cells. We conducted immunohistochemistry, qRT-PCR, and western blotting by using tissue samples from LIHC patients to assess the RANBP3L's diagnostic and prognostic value of LIHC.
Results
In 18 different cancers, RANBP3L expression was found to be lower in tumor tissues compared to normal tissues, including LIHC. Lower RANBP3L expression was related to shorter OS, DSS, and PFI in LIHC. ROC analysis and the nomogram model based on RANBP3L expression demonstrated high predictive accuracy for patient diagnosis and survival. Moreover, immune infiltration analysis showed that RANBP3L was related to various immune cells and impacted prognosis. Furthermore, analysis of LIHC patient tissues found that higher RANBP3L expression was related to better tumor-free survival and OS.
Conclusion
RANBP3L plays a crucial role in LIHC. Not only does its expression level correlate with patient survival, but it also plays an important role in immune modulation. RANBP3L presents a promising candidate for future therapeutic strategies and a biomarker for LIHC.
{"title":"The Role of RANBP3L in Pan-Cancer With Its Significance in Hepatocellular Carcinoma","authors":"Beini Cen, Jie Li, Chao Wang","doi":"10.1002/cnr2.70440","DOIUrl":"10.1002/cnr2.70440","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>RAN binding protein 3-like (RANBP3L), a member of the Ran-binding protein family, has been linked to various cellular functions, but the role in cancer remains underexplored. In this research, we assessed the diagnostic and prognostic value of RANBP3L in pan-cancer, especially in liver hepatocellular carcinoma (LIHC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to explore the pan-cancer expression, prognostic value, and immune-related roles of RANBP3L, especially emphasis on validating its diagnostic and prognostic significance in hepatocellular carcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed RANBP3L expression of 33 cancer types from TCGA data and assessed its relationship with overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). We used TIMER2.0 and CIBERSORT to explore the correlation between RANBP3L expression and immune cells. We conducted immunohistochemistry, qRT-PCR, and western blotting by using tissue samples from LIHC patients to assess the RANBP3L's diagnostic and prognostic value of LIHC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 18 different cancers, RANBP3L expression was found to be lower in tumor tissues compared to normal tissues, including LIHC. Lower RANBP3L expression was related to shorter OS, DSS, and PFI in LIHC. ROC analysis and the nomogram model based on RANBP3L expression demonstrated high predictive accuracy for patient diagnosis and survival. Moreover, immune infiltration analysis showed that RANBP3L was related to various immune cells and impacted prognosis. Furthermore, analysis of LIHC patient tissues found that higher RANBP3L expression was related to better tumor-free survival and OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RANBP3L plays a crucial role in LIHC. Not only does its expression level correlate with patient survival, but it also plays an important role in immune modulation. RANBP3L presents a promising candidate for future therapeutic strategies and a biomarker for LIHC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848861","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}
Aytak Vahdat Khajeh Pasha, Mohammad Esfandiyari, Alireza Parnian, Mohammad Mahboubi-Rabbani, Maryam Bayanati
Background
The rising global incidence of Helicobacter pylori-related diseases, particularly gastric cancer, underscores the urgent need for effective preventive vaccines, motivating the exploration of innovative immunoinformatic strategies to address this public health challenge.
Aims
The aim of this study was to design a multi-epitope subunit vaccine for Helicobacter pylori using an immunoinformatics approach. Specifically, the objectives were to predict potential epitopes from the flagellin B and urease B proteins, integrate the cholera toxin B subunit (CTB) as a mucosal adjuvant, and perform computational validation of the vaccine construct for antigenicity, stability, and interaction with immune receptors.
Methods
This study utilized an immunoinformatics approach to design a multi-epitope subunit vaccine, involving epitope prediction from flagellin B and urease B, integration of the cholera toxin B subunit (CTB) as a mucosal adjuvant, and computational validation through tools like VaxiJen, Phyre2, MolProbity, and HDOCK for antigenicity, structure, and docking analysis.
Results
The resulting vaccine construct comprises 406 amino acids with a molecular weight of 43 424.77 Da, exhibiting a predicted antigenic score of 1.0084, non-allergenic and non-toxic properties, and a stable physiochemical profile (instability index 23.51, GRAVY −0.425). Structural analysis suggested 99.1% (525/530) of residues in favored Ramachandran regions and 100.0% in allowed regions. Molecular docking with Toll-like receptor 5 (TLR5) indicated a superior docking score of −309.05 and a confidence score of 0.9601, outperforming TLR2 (−250.74), with 10 CTL epitopes (6 from flagellin B, 4 from urease B), 6 HTL epitopes, and 2 LBL epitopes linked by AAY, GPGPG, and KK linkers, respectively.
Conclusion
This research provides a computationally optimized vaccine design that shows potential for eliciting immune responses against H. pylori. Importantly, the findings remain entirely theoretical and require rigorous experimental validation in vitro and in vivo to assess their immunological relevance, safety, and efficacy before any translational or clinical application can be considered.
{"title":"Immunoinformatics-Based Multi-Epitope Vaccine Targeting Helicobacter Pylori","authors":"Aytak Vahdat Khajeh Pasha, Mohammad Esfandiyari, Alireza Parnian, Mohammad Mahboubi-Rabbani, Maryam Bayanati","doi":"10.1002/cnr2.70441","DOIUrl":"10.1002/cnr2.70441","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The rising global incidence of <i>Helicobacter pylori</i>-related diseases, particularly gastric cancer, underscores the urgent need for effective preventive vaccines, motivating the exploration of innovative immunoinformatic strategies to address this public health challenge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study was to design a multi-epitope subunit vaccine for Helicobacter pylori using an immunoinformatics approach. Specifically, the objectives were to predict potential epitopes from the flagellin B and urease B proteins, integrate the cholera toxin B subunit (CTB) as a mucosal adjuvant, and perform computational validation of the vaccine construct for antigenicity, stability, and interaction with immune receptors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study utilized an immunoinformatics approach to design a multi-epitope subunit vaccine, involving epitope prediction from flagellin B and urease B, integration of the cholera toxin B subunit (CTB) as a mucosal adjuvant, and computational validation through tools like VaxiJen, Phyre2, MolProbity, and HDOCK for antigenicity, structure, and docking analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The resulting vaccine construct comprises 406 amino acids with a molecular weight of 43 424.77 Da, exhibiting a predicted antigenic score of 1.0084, non-allergenic and non-toxic properties, and a stable physiochemical profile (instability index 23.51, GRAVY −0.425). Structural analysis suggested 99.1% (525/530) of residues in favored Ramachandran regions and 100.0% in allowed regions. Molecular docking with Toll-like receptor 5 (TLR5) indicated a superior docking score of −309.05 and a confidence score of 0.9601, outperforming TLR2 (−250.74), with 10 CTL epitopes (6 from flagellin B, 4 from urease B), 6 HTL epitopes, and 2 LBL epitopes linked by AAY, GPGPG, and KK linkers, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This research provides a computationally optimized vaccine design that shows potential for eliciting immune responses against <i>H. pylori</i>. Importantly, the findings remain entirely theoretical and require rigorous experimental validation in vitro and in vivo to assess their immunological relevance, safety, and efficacy before any translational or clinical application can be considered.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848853","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}
Pragati Patharia, B. Surya Prasad Rao, Prabira Kumar Sethy, Ashoka Kumar Ratha, Aziz Nanthaamornphong
Background and Aim
The worldwide healthcare system faces significant challenges due to the increasing prevalence of lung and colon cancer, highlighting the need for timely and accurate detection to improve patient prognosis. The precision of cancer diagnosis is highly dependent on the expertise of histopathologists, making it a complex and demanding endeavor. A shortage of sufficiently skilled experts can lead to the ineffective allocation of healthcare resources, potential misdiagnoses, and unwarranted interventions, ultimately threatening patient well-being. However, technological advancements have introduced deep learning as a powerful tool in clinical applications, particularly in the field of medical imaging. This study aims to develop a novel diagnostic method leveraging deep learning techniques to enhance the accuracy of lung and colon cancer detection.
Methods
The study utilized the LC25000 dataset, which comprises 25 000 histopathological images of lung and colon tissue. A novel approach was implemented using a Fast Super-Resolution Convolutional Neural Network (FSRCNN) for image enhancement and a Support Vector Machine (SVM) model based on DenseNet201 for classification. The FSRCNN was employed to improve the clarity and detail of images by increasing their resolution, which is crucial for accurate cancer detection.
Results
The proposed model demonstrated superior performance compared to existing Convolutional Neural Network (CNN) models. It achieved an overall accuracy of 98.00%, precision of 98.10%, sensitivity of 98%, F1 score of 0.98, and specificity of 99.50%. These metrics indicate a significant enhancement in diagnostic accuracy and reliability, underscoring the effectiveness of the FSRCNN and SVM-based DenseNet201 model.
Conclusion
The implementation of the FSRCNN and SVM-based DenseNet201 model provided substantial improvements in the detection of lung and colon cancer, as evidenced by high accuracy and specificity metrics. While the LC25000 dataset offered a solid foundation for this analysis, future research should aim to validate the model's effectiveness using a broader array of diverse and extensive datasets. Additionally, integrating supplementary diagnostic techniques, such as genetic data and electronic health records, could further enhance the model's diagnostic precision and practical application in cancer diagnosis.
{"title":"Enhanced Diagnosis of Lung and Colon Cancer Severity Through Deep Feature Analysis Using DenseNet201 and SVM With Histopathological Images: A Super-Resolution Approach","authors":"Pragati Patharia, B. Surya Prasad Rao, Prabira Kumar Sethy, Ashoka Kumar Ratha, Aziz Nanthaamornphong","doi":"10.1002/cnr2.70439","DOIUrl":"10.1002/cnr2.70439","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>The worldwide healthcare system faces significant challenges due to the increasing prevalence of lung and colon cancer, highlighting the need for timely and accurate detection to improve patient prognosis. The precision of cancer diagnosis is highly dependent on the expertise of histopathologists, making it a complex and demanding endeavor. A shortage of sufficiently skilled experts can lead to the ineffective allocation of healthcare resources, potential misdiagnoses, and unwarranted interventions, ultimately threatening patient well-being. However, technological advancements have introduced deep learning as a powerful tool in clinical applications, particularly in the field of medical imaging. This study aims to develop a novel diagnostic method leveraging deep learning techniques to enhance the accuracy of lung and colon cancer detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study utilized the LC25000 dataset, which comprises 25 000 histopathological images of lung and colon tissue. A novel approach was implemented using a Fast Super-Resolution Convolutional Neural Network (FSRCNN) for image enhancement and a Support Vector Machine (SVM) model based on DenseNet201 for classification. The FSRCNN was employed to improve the clarity and detail of images by increasing their resolution, which is crucial for accurate cancer detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proposed model demonstrated superior performance compared to existing Convolutional Neural Network (CNN) models. It achieved an overall accuracy of 98.00%, precision of 98.10%, sensitivity of 98%, F1 score of 0.98, and specificity of 99.50%. These metrics indicate a significant enhancement in diagnostic accuracy and reliability, underscoring the effectiveness of the FSRCNN and SVM-based DenseNet201 model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The implementation of the FSRCNN and SVM-based DenseNet201 model provided substantial improvements in the detection of lung and colon cancer, as evidenced by high accuracy and specificity metrics. While the LC25000 dataset offered a solid foundation for this analysis, future research should aim to validate the model's effectiveness using a broader array of diverse and extensive datasets. Additionally, integrating supplementary diagnostic techniques, such as genetic data and electronic health records, could further enhance the model's diagnostic precision and practical application in cancer diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809581","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}
Chi Ching Lim, Wai San Wilson Tam, Widanalage Sanjay Prasad De Mel, Siew Ping Lang, Wee Joo Chng, Cinnie Yentia Soekojo, Fang Fang Song, Melissa Gaik Ming Ooi
Objective
The retrospective data analysis on 80 patients from 2018 to 2022 aimed to determine the incidence and clinical outcomes of vitamin D status and myeloma bone disease among newly diagnosed multiple myeloma (MM) patients in Singapore.
Method
Patients' demographics, bone health data and bone disease management were collected. Chi-square test was conducted to compare variables between patients who survived versus those who demised. Survival differences were compared using log-rank analysis and plotted using Kaplan–Meier estimates. Multivariable survival analysis was conducted using Cox Regression.
Results
Fifty-nine (73.8%) patients had myeloma bone disease at diagnosis, and 42 (71.2%) of these patients had skeletal-related adverse events at diagnosis. The compliance to bone health management needs to be optimized, as only 70 patients had their vitamin D level tested at diagnosis, of which 48 (68.7%) patients were vitamin D insufficient or deficient. Bone disease data did not correlate with mortality. Higher mortality was initially observed among patients with non-Chinese (p = 0.03), R-ISS 3 (p = 0.001), and renal involvement at diagnosis (p = 0.035). R-ISS staging remained the only statistically significant variable after adjusting for race (adjusted HR 3.99; 95% CI 1.58–10.07).
Conclusion
The study found no correlation between myeloma bone health data and survival outcomes in our centre.
{"title":"Incidence and Clinical Outcomes of Vitamin D Status and Myeloma Bone Disease Among Patients With Newly Diagnosed Multiple Myeloma (MM) in a Tropical Country—Retrospective Cohort Study","authors":"Chi Ching Lim, Wai San Wilson Tam, Widanalage Sanjay Prasad De Mel, Siew Ping Lang, Wee Joo Chng, Cinnie Yentia Soekojo, Fang Fang Song, Melissa Gaik Ming Ooi","doi":"10.1002/cnr2.70431","DOIUrl":"10.1002/cnr2.70431","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The retrospective data analysis on 80 patients from 2018 to 2022 aimed to determine the incidence and clinical outcomes of vitamin D status and myeloma bone disease among newly diagnosed multiple myeloma (MM) patients in Singapore.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Patients' demographics, bone health data and bone disease management were collected. Chi-square test was conducted to compare variables between patients who survived versus those who demised. Survival differences were compared using log-rank analysis and plotted using Kaplan–Meier estimates. Multivariable survival analysis was conducted using Cox Regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-nine (73.8%) patients had myeloma bone disease at diagnosis, and 42 (71.2%) of these patients had skeletal-related adverse events at diagnosis. The compliance to bone health management needs to be optimized, as only 70 patients had their vitamin D level tested at diagnosis, of which 48 (68.7%) patients were vitamin D insufficient or deficient. Bone disease data did not correlate with mortality. Higher mortality was initially observed among patients with non-Chinese (<i>p</i> = 0.03), R-ISS 3 (<i>p</i> = 0.001), and renal involvement at diagnosis (<i>p</i> = 0.035). R-ISS staging remained the only statistically significant variable after adjusting for race (adjusted HR 3.99; 95% CI 1.58–10.07).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study found no correlation between myeloma bone health data and survival outcomes in our centre.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809583","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}
Olgu Erkin Çınar, Azade Kanat, Kerim Erer, Rasim Şahin, Esma Eryılmaz Eren, Esra Yıldızhan
Background
Venetoclax-based (ven) combinations have become a standard of care for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, the associated risk of infectious adverse events (IAEs) remains a significant clinical concern.
Aims
This study aimed to evaluate the incidence, characteristics, and risk factors for IAEs in newly diagnosed AML patients treated with venetoclax combinations in a real-world setting.
Methods and Results
We conducted a retrospective cohort study of AML patients treated with ven in combination with hypomethylating agents or low-dose cytarabine (LDAC), with analyses performed on a treatment cycle basis. Clinical and laboratory data, including IAE characteristics, duration of neutropenia, and concomitant medications, were collected, and grade ≥ 2 IAEs were included according to CTCAE v5.0 criteria. The cohort included 143 treatment cycles of 43 patients, with a median neutropenia duration of 13 days (5–35). A total of 34 (23.8%) grade ≥ 2 IAEs occurred, with an incidence of 1 per 121 patient-days. Multivariate analysis identified prolonged neutropenia (days, OR = 1.037, p = 0.005) and interacting concomitant medications (OR = 9.99, p < 0.001) as independent risk factors for IAEs. The rate of invasive fungal infections was as low as 3.5%, and the use of antifungal or antibacterial prophylaxis was not associated with a reduction in the rate of IAEs.
Conclusion
IAEs remain a substantial risk in venetoclax-treated AML patients, particularly during prolonged neutropenia and with concomitant drug interactions. Optimizing venetoclax regimens and careful management of interacting medications may mitigate these risks.
背景：venetoclax为基础的（ven）联合治疗已成为急性髓性白血病（AML）患者不适合强化化疗的标准治疗方案。然而，相关的感染性不良事件（iae）风险仍然是一个重要的临床问题。目的：本研究旨在评估在现实环境中接受venetoclax联合治疗的新诊断AML患者iae的发生率、特征和危险因素。方法和结果：我们对联合低甲基化药物或低剂量阿糖胞苷（LDAC）治疗的AML患者进行了回顾性队列研究，并以治疗周期为基础进行了分析。收集临床和实验室数据，包括IAE特征、中性粒细胞减少持续时间和伴随用药，并根据CTCAE v5.0标准纳入≥2级IAE。该队列包括143个治疗周期的43名患者，中位中性粒细胞减少持续时间为13天（5-35天）。共发生34例(23.8%)≥2级iae，发生率为每121患者天1例。多因素分析确定了中性粒细胞减少延长（天，OR = 1.037, p = 0.005）和联合用药（OR = 9.99, p）。结论：在venetoclax治疗的AML患者中，iae仍然存在很大的风险，特别是在中性粒细胞减少延长和同时存在药物相互作用的情况下。优化venetoclax方案和仔细管理相互作用的药物可以减轻这些风险。
{"title":"Risk Factors for Infectious Adverse Events in Newly Diagnosed Acute Myeloid Leukemia Patients Treated With Venetoclax Combinations: A Retrospective Single-Centre Real-World Experience","authors":"Olgu Erkin Çınar, Azade Kanat, Kerim Erer, Rasim Şahin, Esma Eryılmaz Eren, Esra Yıldızhan","doi":"10.1002/cnr2.70432","DOIUrl":"10.1002/cnr2.70432","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Venetoclax-based (ven) combinations have become a standard of care for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, the associated risk of infectious adverse events (IAEs) remains a significant clinical concern.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to evaluate the incidence, characteristics, and risk factors for IAEs in newly diagnosed AML patients treated with venetoclax combinations in a real-world setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study of AML patients treated with ven in combination with hypomethylating agents or low-dose cytarabine (LDAC), with analyses performed on a treatment cycle basis. Clinical and laboratory data, including IAE characteristics, duration of neutropenia, and concomitant medications, were collected, and grade ≥ 2 IAEs were included according to CTCAE v5.0 criteria. The cohort included 143 treatment cycles of 43 patients, with a median neutropenia duration of 13 days (5–35). A total of 34 (23.8%) grade ≥ 2 IAEs occurred, with an incidence of 1 per 121 patient-days. Multivariate analysis identified prolonged neutropenia (days, OR = 1.037, <i>p</i> = 0.005) and interacting concomitant medications (OR = 9.99, <i>p</i> < 0.001) as independent risk factors for IAEs. The rate of invasive fungal infections was as low as 3.5%, and the use of antifungal or antibacterial prophylaxis was not associated with a reduction in the rate of IAEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IAEs remain a substantial risk in venetoclax-treated AML patients, particularly during prolonged neutropenia and with concomitant drug interactions. Optimizing venetoclax regimens and careful management of interacting medications may mitigate these risks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809577","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}
Ocular adnexal (OA) metastasis from renal cell carcinoma (RCC) is a very rare end-stage entity with a poor prognosis. Reported here is a case of metastatic RCC for which combination therapy with lenvatinib plus pembrolizumab was given for OA metastasis and achieved an excellent response.
Case
A 54-year-old man was referred to our hospital complaining of right eye pain, with a right intraocular tumor showing a maximum diameter of 3 cm subsequently revealed by computed tomography (CT) imaging. Additionally, masses in the right kidney, both lungs, and right iliac bone were noted, while a subsequent percutaneous renal needle biopsy indicated RCC with multiple metastases (cT3aN0M1). Administration of lenvatinib plus pembrolizumab combination therapy was given as first-line treatment, with rapid improvement of the elevated inflammatory response and anemia noted. Findings obtained 17 months following initiation of therapy showed significant shrinkage of the primary and iliac bone lesions, while the OA and lung metastatic lesions had completely disappeared.
Conclusion
These results highlight the potential of lenvatinib plus pembrolizumab combination therapy for the treatment of RCC with OA metastasis, which is generally considered to be an end stage for cancer cases.
{"title":"Successful Combination Therapy With Lenvatinib Plus Pembrolizumab for Rare Case of Advanced Renal Cell Carcinoma With Ocular Adnexal Metastasis","authors":"Yozo Mitsui, Masato Uetani, Fumito Yamabe, Hideyuki Kobayashi, Aki Mitsuda, Naobumi Tochigi, Koichi Nakajima","doi":"10.1002/cnr2.70437","DOIUrl":"10.1002/cnr2.70437","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ocular adnexal (OA) metastasis from renal cell carcinoma (RCC) is a very rare end-stage entity with a poor prognosis. Reported here is a case of metastatic RCC for which combination therapy with lenvatinib plus pembrolizumab was given for OA metastasis and achieved an excellent response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>A 54-year-old man was referred to our hospital complaining of right eye pain, with a right intraocular tumor showing a maximum diameter of 3 cm subsequently revealed by computed tomography (CT) imaging. Additionally, masses in the right kidney, both lungs, and right iliac bone were noted, while a subsequent percutaneous renal needle biopsy indicated RCC with multiple metastases (cT3aN0M1). Administration of lenvatinib plus pembrolizumab combination therapy was given as first-line treatment, with rapid improvement of the elevated inflammatory response and anemia noted. Findings obtained 17 months following initiation of therapy showed significant shrinkage of the primary and iliac bone lesions, while the OA and lung metastatic lesions had completely disappeared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results highlight the potential of lenvatinib plus pembrolizumab combination therapy for the treatment of RCC with OA metastasis, which is generally considered to be an end stage for cancer cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803200","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}
Joseph W. Molloy, Karl Keogh, Mary-Kate McLoughlin, Lauren Devitt, David Lee, Eric Downer, David Robert Grimes, Denis Barry
Background
Neuroblastoma (NB) is a childhood cancer of the sympathetic nervous system, and its prognosis is poor. NB cells undergo transcriptional changes to utilise aerobic glycolysis as their primary metabolic pathway, which provides an immediate source of ATP to meet high biosynthetic demands. Alternative metabolic fuel inputs, including ketone bodies which require oxidative phosphorylation, may impact the proliferative capacity of NB.
Aims
In this exploratory study, the expression of glycolytic and ketolytic genes in the context of MYCN oncogene amplification, tumour staging 1–4 and Kaplan–Meier survivability was investigated using the R2: Genomics analysis and visualisation platform (http://r2.amc.nl), database.
Methods and Results
Three NB genomics datasets were assessed in the R2 platform and further analysed in GraphPad Prism to investigate the relationships between glycolytic and ketolytic gene expression and prognosis. Glycolytic gene expression is increased in MYCN amplified, metastatic tumours and is associated with worse event free survival. Ketolytic gene expression is lower in metastatic tumours and is associated with better event free survivability. The glycolytic gene expression profile of NB suggests that elevated levels correlate with a low probability of survival. Ketolytic gene expression patterns suggest a decreased reliance for ketolytic energy, which may be exploited to slow tumourigenic growth.
Conclusions
This study validates glycolytic and ketolytic gene expression profiles in metastatic and MYCN amplified NB tumours and through conditional analysis suggests the potential use of these genes in prognosis prediction. Furthermore, the study highlights the reliability and utility of genomic databases as oncogenomic tools for NB research.
{"title":"Fuelling Neuroblastoma: Genomic Analysis of Ketolytic and Glycolytic Gene Expression in Relation to MYCN Oncogene Amplification, Stage and Prognosis","authors":"Joseph W. Molloy, Karl Keogh, Mary-Kate McLoughlin, Lauren Devitt, David Lee, Eric Downer, David Robert Grimes, Denis Barry","doi":"10.1002/cnr2.70429","DOIUrl":"10.1002/cnr2.70429","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroblastoma (NB) is a childhood cancer of the sympathetic nervous system, and its prognosis is poor. NB cells undergo transcriptional changes to utilise aerobic glycolysis as their primary metabolic pathway, which provides an immediate source of ATP to meet high biosynthetic demands. Alternative metabolic fuel inputs, including ketone bodies which require oxidative phosphorylation, may impact the proliferative capacity of NB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In this exploratory study, the expression of glycolytic and ketolytic genes in the context of MYCN oncogene amplification, tumour staging 1–4 and Kaplan–Meier survivability was investigated using the R2: Genomics analysis and visualisation platform (http://r2.amc.nl), database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Three NB genomics datasets were assessed in the R2 platform and further analysed in GraphPad Prism to investigate the relationships between glycolytic and ketolytic gene expression and prognosis. Glycolytic gene expression is increased in MYCN amplified, metastatic tumours and is associated with worse event free survival. Ketolytic gene expression is lower in metastatic tumours and is associated with better event free survivability. The glycolytic gene expression profile of NB suggests that elevated levels correlate with a low probability of survival. Ketolytic gene expression patterns suggest a decreased reliance for ketolytic energy, which may be exploited to slow tumourigenic growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study validates glycolytic and ketolytic gene expression profiles in metastatic and MYCN amplified NB tumours and through conditional analysis suggests the potential use of these genes in prognosis prediction. Furthermore, the study highlights the reliability and utility of genomic databases as oncogenomic tools for NB research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12717149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793395","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}
Meghana Maddula, Annelise Decaria, Bea Brown, John Simes, Michael Boyer, Venessa Chin
<div> <section> <h3> Background</h3> <p>Oncogene-driven metastatic non-small cell lung cancer (mNSCLC) is associated with poor survival outcomes, despite advancements in first-line tyrosine kinase inhibitor (TKI) therapies.</p> </section> <section> <h3> Aims</h3> <p>This study aimed to characterise second-line treatment strategies for epidermal growth factor receptor (EGFR)-driven mNSCLC, and to evaluate associated clinical outcomes using real-world data.</p> </section> <section> <h3> Materials</h3> <p>The EnRICH study prospectively collected clinical data on patients diagnosed with lung cancer from NSW, Australia. Patients with EGFR-driven mNSCLC who received second-line therapy following progression on first-line EGFR-TKI were included in this analysis. Outcomes assessed included progression-free survival (PFS2) and overall survival (OS), measured from second-line treatment.</p> </section> <section> <h3> Results</h3> <p>Of 2000 patients with newly diagnosed lung cancer, between 2016 and 2021, 1720 had NSCLC and 679 had metastatic disease. Among these, 647 underwent molecular testing, with 133 harboring an EGFR mutation. Of these 133, 80 patients received first-line TKI therapy. From this group, 68 who subsequently received second-line treatment following disease progression on first-line TKI were included in this analysis. Of these 68 patients, 77% (<i>n</i> = 52/68) were treated with a first- or second-generation TKI (Erlotinib: <i>n</i> = 39, Gefitinib: <i>n</i> = 7, Afatinib: <i>n</i> = 6) in the first-line setting. The remaining 16 patients received the third-generation TKI Osimertinib. Of the total 68 patients in this cohort, in the second-line setting, 45 patients underwent a change in their systemic therapy, and the remaining 23 patients received radiotherapy either with cessation of first-line TKI (<i>n</i> = 11) or in addition to continuation of first-line TKI (<i>n</i> = 12). Of the 45 patients who underwent a change in their systemic therapy, 32 received systemic therapy alone in the second-line setting and 13 received radiotherapy in addition to a change in systemic therapy. Of these 45 patients, 33 received a TKI, with the majority receiving Osimertinib (<i>n</i> = 28). Median PFS2 was 3.0 months (95% CI: 1.32–5.49), with no significant difference between patients treated with second-line TKI and those receiving other therapies (<i>p</i> = 0.24). Median OS was 15.0 months (95% CI: 13.24–23.66) and similarly did not differ significantly between second-line TKI and alternative treatment strategies (<i>p</i> = 0.17).</p>
{"title":"Assessing Second-Line Treatment Strategies and Outcomes in Epidermal Growth Factor Receptor (EGFR) Oncogene-Driven Stage IV Non-Small Cell Lung Cancer, Following a First-Line EGFR-TKI Therapy","authors":"Meghana Maddula, Annelise Decaria, Bea Brown, John Simes, Michael Boyer, Venessa Chin","doi":"10.1002/cnr2.70428","DOIUrl":"10.1002/cnr2.70428","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oncogene-driven metastatic non-small cell lung cancer (mNSCLC) is associated with poor survival outcomes, despite advancements in first-line tyrosine kinase inhibitor (TKI) therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to characterise second-line treatment strategies for epidermal growth factor receptor (EGFR)-driven mNSCLC, and to evaluate associated clinical outcomes using real-world data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials</h3>\u0000 \u0000 <p>The EnRICH study prospectively collected clinical data on patients diagnosed with lung cancer from NSW, Australia. Patients with EGFR-driven mNSCLC who received second-line therapy following progression on first-line EGFR-TKI were included in this analysis. Outcomes assessed included progression-free survival (PFS2) and overall survival (OS), measured from second-line treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 2000 patients with newly diagnosed lung cancer, between 2016 and 2021, 1720 had NSCLC and 679 had metastatic disease. Among these, 647 underwent molecular testing, with 133 harboring an EGFR mutation. Of these 133, 80 patients received first-line TKI therapy. From this group, 68 who subsequently received second-line treatment following disease progression on first-line TKI were included in this analysis. Of these 68 patients, 77% (<i>n</i> = 52/68) were treated with a first- or second-generation TKI (Erlotinib: <i>n</i> = 39, Gefitinib: <i>n</i> = 7, Afatinib: <i>n</i> = 6) in the first-line setting. The remaining 16 patients received the third-generation TKI Osimertinib. Of the total 68 patients in this cohort, in the second-line setting, 45 patients underwent a change in their systemic therapy, and the remaining 23 patients received radiotherapy either with cessation of first-line TKI (<i>n</i> = 11) or in addition to continuation of first-line TKI (<i>n</i> = 12). Of the 45 patients who underwent a change in their systemic therapy, 32 received systemic therapy alone in the second-line setting and 13 received radiotherapy in addition to a change in systemic therapy. Of these 45 patients, 33 received a TKI, with the majority receiving Osimertinib (<i>n</i> = 28). Median PFS2 was 3.0 months (95% CI: 1.32–5.49), with no significant difference between patients treated with second-line TKI and those receiving other therapies (<i>p</i> = 0.24). Median OS was 15.0 months (95% CI: 13.24–23.66) and similarly did not differ significantly between second-line TKI and alternative treatment strategies (<i>p</i> = 0.17).</p>\u0000 ","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767279","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}
Uveal melanoma (UM) is the prevailing malignant tumor that develops within the eye in adults, and it has a bleak outlook because of the few treatment choices available and the high likelihood of returning after treatment. Currently, surgical intervention, radiation therapy, and a combination of both modalities are available therapeutic modalities for controlling UM. However, these techniques are associated with notable adverse effects and have limited efficacy. Therefore, there is a lack of sufficient and reliable therapies for UM, especially for advanced and metastatic UM forms. This review aims to summarize the clinical features and current therapies of UM and highlight recent progress in gene therapy approaches.
Recent Findings
Significant developments in gene therapy have introduced multiple strategies for targeting UM. Gene silencing using siRNA and shRNA has shown efficacy in downregulating oncogenic pathways. CRISPR/Cas9-based editing has enabled selective disruption of tumor-promoting genes, sensitizing tumor cells to targeted inhibitors. Restoration of tumor-suppressive miRNAs has reduced proliferation, migration, and invasion of UM cells in preclinical models. Suicide gene therapy has demonstrated potent cytotoxicity in xenografts. Moreover, oncolytic viruses and stem-cell–associated delivery systems provide novel mechanisms for tumor-selective gene expression and immune activation. Although challenges persist—such as delivery efficiency, immune responses, and genetic heterogeneity—ongoing innovations in vector design, non-viral nanoformulations, and mutation-guided therapies continue to enhance clinical feasibility.
Conclusion
Gene therapy provides improved safety profiles and the possibility of tailored treatment strategies by integrating information on gene expression patterns and DNA alterations. In the future, gene therapy has the potential to improve the treatment of UM by targeting specific genetic mutations driving tumor growth and may offer new hope for patients with advanced stages of UM.
{"title":"Toward Precision Medicine: Gene Therapy Applications in the Management of Uveal Melanoma","authors":"Alireza Azani, Vahid Ghassemifar, Zahra Mehrdad, Maryam Saberivand, Anahid Bagheripour, Safa Tahmasebi, Hossein Gharedaghi, Malihe Sharafi, Hassan Foroozand, Mohammad Saeed Soleimani Meigoli, Saba Pourali, Arash Salmaninejad, Faeze Ahmadi Beni, Qumars Behfar","doi":"10.1002/cnr2.70425","DOIUrl":"10.1002/cnr2.70425","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Uveal melanoma (UM) is the prevailing malignant tumor that develops within the eye in adults, and it has a bleak outlook because of the few treatment choices available and the high likelihood of returning after treatment. Currently, surgical intervention, radiation therapy, and a combination of both modalities are available therapeutic modalities for controlling UM. However, these techniques are associated with notable adverse effects and have limited efficacy. Therefore, there is a lack of sufficient and reliable therapies for UM, especially for advanced and metastatic UM forms. This review aims to summarize the clinical features and current therapies of UM and highlight recent progress in gene therapy approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recent Findings</h3>\u0000 \u0000 <p>Significant developments in gene therapy have introduced multiple strategies for targeting UM. Gene silencing using siRNA and shRNA has shown efficacy in downregulating oncogenic pathways. CRISPR/Cas9-based editing has enabled selective disruption of tumor-promoting genes, sensitizing tumor cells to targeted inhibitors. Restoration of tumor-suppressive miRNAs has reduced proliferation, migration, and invasion of UM cells in preclinical models. Suicide gene therapy has demonstrated potent cytotoxicity in xenografts. Moreover, oncolytic viruses and stem-cell–associated delivery systems provide novel mechanisms for tumor-selective gene expression and immune activation. Although challenges persist—such as delivery efficiency, immune responses, and genetic heterogeneity—ongoing innovations in vector design, non-viral nanoformulations, and mutation-guided therapies continue to enhance clinical feasibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Gene therapy provides improved safety profiles and the possibility of tailored treatment strategies by integrating information on gene expression patterns and DNA alterations. In the future, gene therapy has the potential to improve the treatment of UM by targeting specific genetic mutations driving tumor growth and may offer new hope for patients with advanced stages of UM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 12","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755386","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}
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