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  • Open Access

    REVIEW

    Branched-Chain Amino Acid Metabolic Reprogramming and Cancer: Molecular Mechanisms, Immune Regulation, and Precision Targeting

    Dongchi Cai1,2,#, Jialin Ji3,#, Chunhui Yang1,*, Hong Cai1,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.071152 - 30 December 2025

    Abstract Metabolic reprogramming involving branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—is increasingly recognized as pivotal in cancer progression, metastasis, and immune modulation. This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation, survival, and therapy resistance. Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1 (LAT1) and enzymes including branched chain amino acid transaminase 1(BCAT1), branched chain amino acid transaminase 2 (BCAT2), branched-chain alpha-keto acid dehydrogenase (BCKDH), and branched chain alpha-keto acid dehydrogenase kinase (BCKDK). These alterations sustain energy production, biosynthesis, redox homeostasis, and oncogenic… More >

  • Open Access

    ARTICLE

    miR-512-3p/RPS6KA2 Axis Regulates Cisplatin Resistance in Ovarian Cancer via Autophagy and Ferroptosis

    Jianfa Wu1,2,3, Huang Chen3, Sihong Wang1,2, Lei Peng1,2, Xiaoying Hu1,2, Zhou Liu1,2,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070542 - 30 December 2025

    Abstract Objectives: Ribosomal protein S6 kinase A2 (RPS6KA2) has been identified as a potential prognostic biomarker in several cancers, including breast cancer, glioblastoma, and prostate cancer. However, its functional significance in ovarian cancer is not well characterized. This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer, particularly in relation to cisplatin resistance. Methods: The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR, immunofluorescence staining, immunohistochemistry, and western blotting. Prognostic associations were conducted using the Kaplan-Meier Plotter database.… More >

  • Open Access

    REVIEW

    Effectiveness and Safety of Lenvatinib and Everolimus after Immune Checkpoint Inhibitors in Metastatic Renal Cell Cancer: A Systematic Review

    Giacomo Iovane1,*, Luca Traman2, Michele Maffezzoli1,3, Giuseppe Fornarini2, Domenico Corradi4, Debora Guareschi4, Matteo Santoni5,#, Sebastiano Buti1,#

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070523 - 30 December 2025

    Abstract Background: While the treatment of metastatic renal cell carcinoma (mRCC) is evolving due to immune checkpoint inhibitors (ICIs), optimal strategies for later lines of therapy have yet to be defined. The combination of lenvatinib and everolimus represents a viable option, and the present review aimed to summarize its activity, effectiveness, and safety. Methods: A systematic review of the literature was conducted using PubMed, targeting studies published between 2018 and 2025. Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen. Results:More > Graphic Abstract

    Effectiveness and Safety of Lenvatinib and Everolimus after Immune Checkpoint Inhibitors in Metastatic Renal Cell Cancer: A Systematic Review

  • Open Access

    REVIEW

    The Role of Exosomes as a Key Factor of Cytostatic Resistance in Cancer: Mechanisms of Action, Potential Biomarkers, and Possible Exosome-Based Therapies

    Sandra Kałużna1,*, Monika Świerczewska1,2, Sylwia Ciesiółka1, Małgorzata Partyka1, Michał Nowicki1, Karolina Wojtowicz1

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070356 - 30 December 2025

    Abstract The last research focuses on the role of exosomes in cancer treatment. Exosomes are extracellular vesicles. They can be secreted by cancer cells, and they can modulate chemotherapy sensitivity. Determining exosomal content opens the possibility for guiding treatment strategies for cancer diseases. Exosomal microRNA are considered one of the prime candidates for exosomal biomarkers. Exosomal circular RNAs represent excellent biomarkers for liquid biopsy because of their stability in many types of cancer. Exosomal proteins remain reliable biomarkers also. Exosomes have emerged as promising therapeutic candidates. Their biological properties render them ideal vectors for drug delivery.… More >

  • Open Access

    ARTICLE

    Biological Features of KLC2 Mutations in Chronic Myeloid Leukemia and Their Contribution to Inducing Drug Resistance

    Rabindranath Bera1,#, Yotaro Ochi2,3, Ying-Jung Huang1, Ming-Chung Kuo1,4, Kenichi Yoshida5, Seishi Ogawa2, Lee-Yung Shih1,4,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070259 - 30 December 2025

    Abstract Background: Breakpoint Cluster Region-Abelson (BCR::ABL1) fusion protein is essential in the pathogenesis of chronic myeloid leukemia (CML); however, the chronic-to-blast phase transformation remains elusive. We identified novel kinesin light chain 2 (KLC2) mutations in CML-myeloid blast phase patients. We aimed to examine the functional role of KLC2 mutations in leukemogenesis. Methods: To evaluate the biological role of KLC2 mutants (MT) in CML cells, we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot, immunofluorescence, cell proliferation, differentiation, and apoptosis; Tyrosine kinase inhibitor (TKI)-drug activities; and clonogenic assays for in vitro functional analyses. We co-expressed KLC2-MTMore >

  • Open Access

    ARTICLE

    STC2+ Malignant Cell State Associated with EMT, Tumor Microenvironment Remodeling, and Poor Prognosis Revealed by Single-Cell and Spatial Transcriptomics in Colorectal Cancer

    Kai Gui1,#, Tianyi Yang1,#, Chengying Xiong1, Yue Wang1, Zhiqiang He1, Wuxian Li2,3,*, Min Tang1,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070143 - 30 December 2025

    Abstract Objectives: The mechanism by which specific tumor subsets in colorectal cancer (CRC) use alternative metabolic pathways, particularly those modulated by hypoxia and fructose, to alter the tumor microenvironment (TME) remains unclear. This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach. Methods: Leveraging bulk datasets, single-cell RNA sequencing, and integrative spatial transcriptomics, we developed a prognostic model based on hypoxia-and fructose metabolism-related genes (HFGs) to delineate tumor cell subpopulations and their intercellular signaling networks. Results: We identified a specific subset of stanniocalcin-2 positive (STC2+)… More > Graphic Abstract

    STC2+ Malignant Cell State Associated with EMT, Tumor Microenvironment Remodeling, and Poor Prognosis Revealed by Single-Cell and Spatial Transcriptomics in Colorectal Cancer

  • Open Access

    ARTICLE

    Integrative Multi-Omics Analysis and Experiments Validation Identify COX5B as a Novel Therapeutic Target for Lung Adenocarcinoma

    Lv Ling1,#, Minying Lu2,#, Ling Ye3, Yuanhang Chen2, Sheng Lin2, Jun Yang2, Yu Rong2,*, Guixiong Wu4,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.069889 - 30 December 2025

    Abstract Background: A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies, making the search for new treatment strategies extremely urgent. In this study, we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma (LUAD). Methods: We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B (COX5B) in LUAD. Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD. To further elucidate the role of COX5B in LUAD, we utilized… More > Graphic Abstract

    Integrative Multi-Omics Analysis and Experiments Validation Identify COX5B as a Novel Therapeutic Target for Lung Adenocarcinoma

  • 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

    REVIEW

    Ferroptosis: Mechanisms, Comparison with Cuproptosis and Emerging Horizons in Therapeutics

    Shujie Yin1, Zong Li1, Wen-Bin Ou1,2,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.069049 - 30 December 2025

    Abstract Ferroptosis is an iron-dependent, excessive lipid peroxidation-driven form of regulated cell death. The core mechanisms of ferroptosis include lipid peroxidation cascade, System Xc-glutathioneglutathione peroxidase 4 axis, iron and lipid metabolism chaos, the NAD(P)Hferroptosis suppressor protein 1—ubiquinone axis, and GTP cyclohydrolase 1 tetrahydrobiopterin-dihydrofolate reductase axis. Cuproptosis is triggered by copper ions and involves ferredoxin 1-mediated aggregation of lipoylated proteins, differing fundamentally from ferroptosis. Both ferroptosis and cuproptosis exhibit dual roles (promote or inhibit) in cancers. And the sensitivity of different cancer types to ferroptosis varies, which may depend on special metabolic signatures (e.g., E-cadherin loss causes epithelial–mesenchymal More > Graphic Abstract

    Ferroptosis: Mechanisms, Comparison with Cuproptosis and Emerging Horizons in Therapeutics

  • Open Access

    ARTICLE

    P2RX1 Influences the Prognosis of Ph+/Ph-Like ALL through Energy and Calcium Metabolism

    Xiangmei Ye1,2,3, Baoyi Yang4, Xin Zhang5, Luyuan Yang1, Likun Zhang5, Qin Ren1, Xiaobing Li1, Leiguang Feng1, Lanlan Wei3,6,7,*, Peng Song1, Yuqing Ye8, Xin Lian9, Yujuan Gao9, Haidi Tang1, Zhiyu Liu1

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.068814 - 30 December 2025

    Abstract Objectives: Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia (Ph+/Ph-like ALL) constitute the majority of relapsed/refractory B-ALL (R/R B-ALL) cases, highlighting an urgent need to discover new therapeutic targets. This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays, with the goal of informing new clinical treatment strategies. Results: Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1 (P2RX1) was associated with unfavorable outcomes. Specifically, patients with poor prognosis and low P2RX1 expression exhibited downregulation of… More >

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