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  • Open Access

    ARTICLE

    SDHA Deficiency in Hepatocellular Carcinoma Promotes Tumor Progression through Succinate-Induced M2 Macrophage Polarization

    Xinyang Li1,2,3,#, Luyuan Ma1,2,3,#, Chuan Shen1,2,3, Ruolan Gu1,2,3, Shilong Dong1,2,3, Mingjie Liu1,2,3, Ying Xiao1,2,3, Wenpeng Liu1,2,3, Yuexia Liu1,2,3, Caiyan Zhao1,2,3,*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.073179 - 19 January 2026

    Abstract Background: Hepatocellular carcinoma (HCC) is an aggressive and lethal malignancy. Metabolic reprogramming dynamically remodels the tumor microenvironment (TME) and drives HCC progression. This study investigated the mechanism through which metabolic reprogramming remodels the TME in HCC. Methods: HCC patient transcriptome data were subjected to bioinformatics analysis to identify differentially expressed genes and immune infiltration status. Immunohistochemical analysis was performed to determine the correlation between succinate dehydrogenase complex subunit A (SDHA) expression and M2 macrophage infiltration. SDHA-knockdown or SDHA-overexpressing HCC cells were used for in vitro experiments, including co-culturing, flow cytometry, and enzyme-linked immunosorbent assay. Western blotting… More >

  • Open Access

    REVIEW

    A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy

    Harpreet Kaur1,*, Dhrubalochan Rana2, Sowvik Bag2, Paramjeet Singh3

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.071209 - 19 January 2026

    Abstract The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic regulators emphasize their promise in advancing precision medicine. However, in many cases, the resistance mechanisms associated with these interventions… More > Graphic Abstract

    A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy

  • Open Access

    ARTICLE

    Real-World Outcomes of First-Line Palbociclib Plus Endocrine Therapy for HR+/HER2− Metastatic Breast Cancer in Japan: A Single-Center Retrospective Study

    Keiko Yanagihara1,*, Masato Yoshida2, Kensaku Awaji2, Tamami Yamakawa1, Sena Kato1, Miki Tamura1, Koji Nagata3

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.073891 - 30 December 2025

    Abstract Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have transformed the management of hormone receptor–positive/HER2–negative (HR+/HER2–) advanced breast cancer, yet evidence for elderly or poor-performance patients remains limited. This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients, with additional subgroup analyses by age and performance status. Methods: We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2− breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), disease control rate (DCR), and safety.… More >

  • Open Access

    ARTICLE

    Early GLP-1 Agonist Use and Cancer Risk in Type 2 Diabetes: A Real-World Data Cohort Study

    Cheng-Hsun Chuang1,2,3,#, Ping-Kun Tsai3,4,5,6,#, Shih-Wen Kao7,8, Yu-Hsun Wang8,9,*, Chao-Bin Yeh1,2,3,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.072875 - 30 December 2025

    Abstract Background: To determine whether initiating a glucagon-like peptide-1 receptor agonist (GLP-1 RA) within 3 months of type 2 diabetes (T2DM) diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index (BMI). Methods: This retrospective cohort study used electronic health records from the TriNetX U.S. research network. Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis. Following 1:1 propensity score matching, both the GLP-1 RA user and non-user… More > Graphic Abstract

    Early GLP-1 Agonist Use and Cancer Risk in Type 2 Diabetes: A Real-World Data Cohort Study

  • Open Access

    ARTICLE

    Application Value and Research Frontiers of Immunotherapy in Glioblastoma: A Bibliometric and Visualized Analysis

    Kun Deng1,2,3, Jianliang Huang1,2,3, Danyang Li2,3, Wei Gao2,3, Minghua Wu2,3,4,*, Mingsheng Lei1,5,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.069442 - 30 December 2025

    Abstract Background: Glioblastoma (GBM) prognosis has seen little improvement over the past two decades. While immunotherapy has revolutionized cancer treatment, its impact on GBM remains limited. To characterize the evolving research landscape and identify future directions in GBM immunotherapy, we conducted a comprehensive bibliometric review. Methods: All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection. CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data. Results: Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions, published in… More >

  • Open Access

    ARTICLE

    CXCR1 and CXCR2 Antagonism with G31P Attenuates Chemotherapy-Induced Lung Inflammation and Augments the Gefitinib Therapeutic Response in Lung Cancer

    Muhammad Noman Khan1,2,3,*, Kang Tian2, John R. Gordon4, Fang Li2, Song-Ze Ding1,*

    Oncology Research, Vol.33, No.12, pp. 3837-3854, 2025, DOI:10.32604/or.2025.069408 - 27 November 2025

    Abstract Objectives: Chemotherapy-induced lung inflammation limits the efficacy of anticancer therapies such as gefitinib in non-small cell lung cancer (NSCLC). Glutamic acid-leucine-arginine positive (ELR+) CXC chemokines and their receptors, CXC chemokine receptor 1 and 2 (CXCR1 and CXCR2), mediate both inflammatory responses and tumor progression. This study evaluated the effects of CXCR1/2 antagonism by G31P, a CXC motif chemokine ligand 8 (CXCL8)-mutated peptide, alone or in combination with gefitinib, on lung cancer growth and chemotherapy-induced pulmonary inflammation. Methods: Human NSCLC cell lines (A549 and H460) were treated with gefitinib and/or G31P. Cell proliferation, apoptosis, and signaling… More > Graphic Abstract

    CXCR1 and CXCR2 Antagonism with G31P Attenuates Chemotherapy-Induced Lung Inflammation and Augments the Gefitinib Therapeutic Response in Lung Cancer

  • Open Access

    ARTICLE

    DADS Regulates EMT and Chemotherapy Resistance by Inhibiting RORα/β-Catenin Signaling through PKCα-Dependent Phosphorylation in Gastric Cancer

    Yizhen Zhang1,2,#, Juan Li1,3,#, Huanqing Liu1,4,#, Hong Xia1, Jian Su1,5, Fang Liu1, Bo Su6,*, Qi Su1,*

    Oncology Research, Vol.33, No.12, pp. 3869-3886, 2025, DOI:10.32604/or.2025.068689 - 27 November 2025

    Abstract Objectives: Gastric cancer (GC) is often associated with high invasiveness, epithelial-mesenchymal transition (EMT), and resistance to 5-fluorouracil (5-FU), highlighting the need for novel therapeutic targets. This study explored whether diallyl disulfide (DADS) upregulates retinoic acid-related orphan receptor alpha (ROR) to weaken the protein kinase C alpha (PKC)/RORα-mediated RORα/β-catenin pathway, thereby inhibiting GC cell invasion, epithelial-mesenchymal transition (EMT), and enhancing 5-FU sensitivity. Methods: Human GC cell lines MGC-803 and SGC7901 were treated with DADS, RORα agonist SR1078/antagonist T0901317, and PKCα agonist TPA/antagonist GO6976. Cell proliferation (MTT), migration (scratch assay), invasion (Transwell), protein expression (Western blot), protein… More >

  • Open Access

    ARTICLE

    Targeting HER2-Positive HCC1954 Breast Cancer Cells by Novel Thiazole-Dihydrobenzisoxazoles: In-Depth Design, Synthesis and Initial In Vitro Study

    Yuri A. Piven1, Danila V. Sorokin2, Nastassia A. Varabyeva1, Alexandra L. Mikhaylova2, Fedor B. Bogdanov2, Elena V. Shafranovskaya1, Raman M. Puzanau3, Fedor A. Lakhvich1, Alexander M. Scherbakov2,4,*

    Oncology Research, Vol.33, No.12, pp. 4049-4072, 2025, DOI:10.32604/or.2025.067832 - 27 November 2025

    Abstract Background: The most aggressive forms of breast cancer are characterized by independence from steroid hormones but a strong dependence on growth factors. In such cancer cells, oncogenic receptors, including human epidermal growth factor receptor 2 (HER2), are activated, and their targeted inhibition represents an attractive therapeutic strategy. The study aimed to develop small-molecule potential dual heat shock protein 90 (HSP90)-HER2 inhibitors and evaluate them as anticancer agents in HER2-positive cells. Methods: The research project involved obtaining a series of compounds with potential dual inhibitory activity against HSP90 and HER2 by targeted organic synthesis, which was… More > Graphic Abstract

    Targeting HER2-Positive HCC1954 Breast Cancer Cells by Novel Thiazole-Dihydrobenzisoxazoles: In-Depth Design, Synthesis and Initial <i>In Vitro</i> Study

  • Open Access

    REVIEW

    Universal CAR-T Cell Therapy for Cancer Treatment: Advances and Challenges

    Jianan Lei*, Zhuona Ni, Ruidi Zhang

    Oncology Research, Vol.33, No.11, pp. 3347-3373, 2025, DOI:10.32604/or.2025.067445 - 22 October 2025

    Abstract This review aims to explore the development, challenges, and future directions of UCAR cell therapy as a scalable alternative to autologous CAR-T for cancer treatment. Consequently, limitations of autologous CAR-T, including long production, variable quality, and cost, drive off-the-shelf UCAR development to standardize manufacturing and improve access. Current UCAR-T cell strategies focus on mitigating the risks of graft-vs.-host disease and host-vs.-graft rejection through advanced gene editing technologies, including clustered regularly interspaced short palindromic repeat-associated system Cas9-mediated knockout of the T cell receptor, human leukocyte antigen, and cluster of differentiation 52 (CD52). Beyond conventional T cells, cell… More >

  • Open Access

    ARTICLE

    Investigation on the Anti-Cancer Effects of HER2-Targeted CAR-T Cells Engineered Using the PiggyBac Transposon System

    Tian-Tian Li1,2,3,#, Ming-Yao Meng1,2,4,#, Zheng Yu5, Yang-Fan Guo1,2,4, Yi-Yi Zhao1,2,4, Hui Gao1,2,4, Li-Li Yang1,2,3, Li-Rong Yang1,2,3, Meng-Yuan Chu1,2,3, Shan He1,2,4, Yuan Liu1,2,4, Xiao-Dan Wang1,2,4, Wen-Ju Wang1,2,4, Zong-Liu Hou1,2,4, Li-Wei Liao1,2,4,*, Lin Li1,2,4,*

    Oncology Research, Vol.33, No.11, pp. 3447-3467, 2025, DOI:10.32604/or.2025.065394 - 22 October 2025

    Abstract Background: Chimeric antigen receptor T (CAR-T) cell therapies have demonstrated significant clinical efficacy in hematological malignancies. However, their application to solid tumors remains substantially limited by multiple challenges, including the risk of off-target effects. Hence, optimizing CAR-T cells for stronger antigen binding is essential. Methods: In this study, we employed a classical anti-human endothelial growth factor receptor 2 (HER2) single-chain variable fragment (scFv) derived from trastuzumab, alongside an anti-HER2-13 scFv identified from a combinatorial cellular CAR library, for the construction of a third-generation CAR-T cell. Meanwhile, the phenotypes and both in vitro and in vivo functions of… More > Graphic Abstract

    Investigation on the Anti-Cancer Effects of HER2-Targeted CAR-T Cells Engineered Using the <i>PiggyBac</i> Transposon System

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