Hikmat Abdel-Razeq,1,2 Malek Horani,1 Faris Tamimi,1 Tamer Al-Batsh,1 Osama El Khatib,1 Yosra Almasri,1 Ameed Sameer Ghanem,1 Qutaiba Jawarneh,1 Maram Ismat Al-yag’oub,1 Adel Yousef Jaffal,1 Rnad Khader,1 Asala Alanani,1 Baha Sharaf,1 Maryam El-Atrash,1 Tala Abuhamdah,1 Ayat Taqash11Section of Hematology and Medical Oncology, Department of Internal Medicine, King Hussein Cancer Center, Amman, 11941, Jordan; 2School of Medicine, The University of Jordan, Amman, 11941, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, 202 Queen Rania Al Abdullah Street, Amman, 11941, Jordan, Tel +962-6 5300460 Ext. 1000, Email habdelrazeq@khcc.joPurpose: Adjuvant CDK4/6 inhibitors have demonstrated significant disease-free survival (DFS) benefits in high-risk early-stage hormone receptor (HR)-positive /HER2-negative breast cancer. However, real-world outcome data describing patients who would meet contemporary eligibility criteria remain limited. This study evaluates treatment outcomes in patients retrospectively classified as eligible for adjuvant ribociclib treatment.Patients and Methods: A retrospective cohort analysis was conducted using clinical data from patients with early-stage HR-positive/HER2-negative breast cancer. Eligibility for adjuvant ribociclib was assigned using the NATALEE trial-based criteria. Differences in treatment outcomes in those eligible versus ineligible patients are reported.Results: Among the 2730 patients included, 1,955 (71.6%) were high risk and would have met NATALEE eligibility, including 1,679 (85.9%) with node-positive disease, 602 (30.8%) with cT3-4 tumors, and 686 (35.1%) with grade 3 disease; 775 (28.4%) were ineligible due to lower-risk features. Across the cohort, the 5-year DFS rate was significantly worse in CDK4/6i-eligible patients compared to those deemed ineligible: 78.4% versus 91.5% (HR=2.51; 95% CI: 2.01– 3.14; p< 0.0001). Though median OS was not reached, survival curve separation became evident by 36 months and widened progressively. Multivariable Cox regression identified low/intermediate ER expression (< 50%), node-positive disease, larger tumors (cT3-4), and grade 3 histology as independent predictors of worse overall survival. Low/intermediate ER expression was associated with significantly poorer OS (HR 1.85, 95% CI 1.27– 2.70; p=0.001), while lower-grade and smaller tumors were associated with improved survival.Conclusion: A significant proportion of patients in this real-world cohort would have met criteria for adjuvant CDK4/6 inhibition. These patients experienced worse survival outcomes compared to their ineligible counterparts. These findings provide real-world historical outcome data for patients who would now be considered candidates for adjuvant ribociclib and may serve as a benchmark for evaluating outcomes following adoption of adjuvant ribociclib.Keywords: early-stage breast cancer, hormone receptor-positive, HER2-negative, CDK4/6 inhibitors, ribociclib
Monde Ntwasa, Sibusiso MalindisaDepartment of Life and Consumer Sciences, University of South Africa, Johannesburg, South AfricaCorrespondence: Monde Ntwasa, Department of Life and Consumer Sciences, University of South Africa, Johannesburg, South Africa, Tel +27 11 471 2272, Email ntwasmm@unisa.ac.zaPurpose: The Ezetimibe-curcumin combination (Ezercumin™) is a new anticancer drug developed from the approved drug ezetimibe, combined with curcumin as a protein kinase inhibitor. Ezetimibe is an FDA-approved orally administered drug that blocks intestinal cholesterol uptake, thereby reducing plasma cholesterol levels. Previous studies in our lab showed that ezetimibe binds the MDM2-p53 binding domain and may reactivate p53 in cancers. However, ezetimibe is rapidly metabolized via glucuronidation, limiting its anticancer potential. Curcumin, a known kinase inhibitor, was evaluated for its ability to preserve ezetimibe’s active form and enhance its antitumor effect.Methods: We assessed the effects of ezetimibe, curcumin, and their combination on cell viability and cell-cycle progression in CRC cell lines (HCT116, HT-29, and SW620) using xCELLigence technology and flow cytometry. Pharmacokinetics and antitumor efficacy were evaluated in non-tumor-bearing and orthotopic HCT116_Luc xenograft NMRI nude mice in collaboration with Reaction Biology.Results: Ezetimibe alone induced a marked reduction in the HCT116 cell index, ~70% apoptosis, and a G0/G1 arrest, whereas curcumin alone showed minimal cytotoxicity. In p53-mutant HT-29 and SW620 cells, treatments had no significant effect, reinforcing p53-dependent sensitivity. In vivo early pharmacokinetics showed rapid clearance of ezetimibe and curcumin in co-administration. In the orthotopic CRC model, the combination of ezetimibe and curcumin was associated with modest late reduction in tumour bioluminescence from day 47 onward, indicating tumour size reduction that was not seen with ezetimibe treatment alone during the post-treatment observation period.Conclusion: The ezetimibe–curcumin combination reduces tumor burden in vivo, demonstrating its therapeutic potential. These preliminary findings suggest the ezetimibe-curcumin combination as a potential anticancer therapeutic and support further studies with optimized dosing and schedules. Currently, an in vivo preclinical study using holofibre technology is underway to determine pharmacokinetics and assess treatment effectiveness across several cancer types, with particular focus on Mdm2-overexpressing cancers.Keywords: ezetimibe, colorectal cancer, mouse double minute, Mdm2, ezercumin, anticancer drugs
Yao Z, Sun B, Hong Q, et al. Drug Des Devel Ther. 2015;9:5911—5923. https://doi.org/10.2147/DDDT.S86881 We, the Editors and Publisher of the journal Drug Design, Development and Therapy, have retracted the published article. After publication, concerns have been raised by a third party in 2025 about the integrity of the data in Figure 3 of the article. Further investigation conducted by the Journal and Publisher confirmed the following: Unusual similarities present in the image panels representative of different samples and conditions in Figure 3. Unexpected overlaps between Western blots in Figure 7 with Western blots in the following article:Zhao X, Hua Y, Chen H, Yang H, Zhang T, Huang G, Zhou Y. Aldehyde dehydrogenase-2 protects against myocardial infarction-related cardiac fibrosis through modulation of the Wnt/β-catenin signaling pathway. Therapeutics and Clinical Risk Management. 2015;11:1371–1381. https://doi.org/10.2147/TCRM.S88297 When approached for an explanation, the authors did not respond to the queries raised by the Journal and Publisher. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Kuang-Ming Liao,1,2 Sheng-Chi Huang,3 Jheng-Yan Wu,4,5 Chia-Yu Kuo,3 Wan-Hsuan Hsu,6 Konstantinos Kostikas,7 Chih-Cheng Lai8,91Department of Internal Medicine, Chi Mei Hospital, Chiali, Taiwan; 2Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan, Taiwan; 3Department of General Medicine, Chi Mei Medical Center, Tainan, Taiwan; 4Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan; 5Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 7Respiratory Medicine Department, University of Ioannina, Ioannina, Greece; 8Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; 9School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, TaiwanCorrespondence: Chih-Cheng Lai, Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan, Email dtmed141@gmail.comBackground: Dupilumab, mepolizumab, and benralizumab have each demonstrated efficacy in placebo-controlled trials for chronic obstructive pulmonary disease (COPD) with type 2 inflammation. However, no head-to-head trials or real-world comparative effectiveness studies have been reported. We aimed to compare the effectiveness of dupilumab, mepolizumab, and benralizumab in patients with COPD using propensity score-matched cohort analyses.Design: Retrospective cohort study using the TriNetX US Collaborative Network.Methods: Adults with COPD initiating dupilumab, mepolizumab, or benralizumab between 2022 and 2025 were identified. Biologic-naive new users were included in two pairwise comparisons: dupilumab versus mepolizumab and dupilumab versus benralizumab. Propensity score matching (1:1) balanced baseline characteristics. The primary outcome was COPD exacerbation; secondary outcomes included acute respiratory failure, pneumonia, and bronchitis over 365 days. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.Results: Propensity score matching identified 3078 dupilumab–mepolizumab pairs and 2109 dupilumab–benralizumab pairs. Compared with mepolizumab, dupilumab was associated with a numerically lower risk of COPD exacerbation (HR, 0.76; 95% CI, 0.57– 1.01) and a significantly lower risk of bronchitis (HR, 0.69; 95% CI, 0.49– 0.98). No significant differences were observed between dupilumab and benralizumab for COPD exacerbation (HR, 0.98; 95% CI, 0.70– 1.40), acute respiratory failure, pneumonia, or bronchitis.Conclusion: In this large real-world cohort study, no statistically significant difference in COPD exacerbation risk was observed between dupilumab and mepolizumab or between dupilumab and benralizumab. However, blood eosinophil counts and baseline lung function measurements were not available in the dataset, so residual confounding cannot be excluded.Keywords: chronic obstructive pulmonary disease, biologic therapy, dupilumab, mepolizumab, benralizumab
