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  • Open Access

    ARTICLE

    miR-152-3p Overcomes Temozolomide Resistance in Glioblastoma by Targeting TGF-α and Enhancing Apoptosis

    Chun-Nun Chao1,2, Chiung-Yao Fang2,3, Chia-Hsin Hou1, Jen-Tsung Yang4,5, Yu-Ping Wu4,6, Jui-Chieh Chen6,*
    Oncology Research, DOI:10.32604/or.2026.083962
    (This article belongs to the Special Issue: Molecular Targeting Therapy for Anticancer Treatment)
    Abstract Objectives: Temozolomide (TMZ) resistance remains a major challenge in glioblastoma (GBM) treatment. This study investigated the role of miR-152-3p and its downstream target, transforming growth factor-α (TGF-α), in regulating TMZ sensitivity in GBM. Methods: Public GEO and CGGA datasets were analyzed to evaluate the expression and prognostic significance of miR-152-3p. TMZ-resistant GBM cell lines (U87MGR and DBTRG-05MGR) were established by continuous TMZ exposure. Gain- and loss-of-function experiments were performed using miR-152-3p mimics and inhibitors. Cell viability, apoptosis, and TGF-α expression were assessed by MTT, qRT-PCR, and Western blot analyses. Results: miR-152-3p expression was significantly decreased in recurrent… More >

  • Open Access

    CASE REPORT

    Prolonged Disease Stability with Durvalumab and Tremelimumab Rechallenge Following Prior Immune Checkpoint Inhibitors: A Case Report

    Waseem Abdelrahim1, Ebtesam Al-Najjar2, Seif El Beheary3, Abdullah Esmail2,*
    Oncology Research, DOI:10.32604/or.2026.083193
    (This article belongs to the Special Issue: Advances in Cancer Immunotherapy)
    Abstract Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a leading cause of cancer-related mortality worldwide due to frequent recurrence and early metastasis. While immune checkpoint inhibitor (ICPI)-based regimens have revolutionized the treatment landscape for advanced HCC, clinical evidence regarding the safety and efficacy of ICPI rechallenge following disease progression or severe immune-related adverse events (irAEs) remains sparse. This report describes a case of prolonged disease stability achieved through sequential immunotherapy using durvalumab and tremelimumab (Durva/Treme) after prior ICPI failure and high-grade toxicity. Case Description: A 65-year-old male with recurrent stage IV… More >

  • Open Access

    ARTICLE

    PSMB9 Promotes the Malignant Progression of Colorectal Cancer by Regulating the PI3K/Akt Pathway

    Wen Gao1,2, Xingyu Zheng1,2, Yanan Hu1,2, Rui Zou3, Yongan Zhou4, Xiang Song2,*
    Oncology Research, DOI:10.32604/or.2026.082652
    (This article belongs to the Special Issue: Identification of potential targets and biomarkers for cancers and the exploration of novel molecular mechanisms of tumorigenesis and metastasis)
    Abstract Background: As a core component of the immunoproteasome, the β1i subunit (proteasome 20S subunit beta 9, PSMB9) is involved in antigen processing and presentation and regulates anti-tumor immune responses. PSMB9 is aberrantly overexpressed in colorectal cancer. However, the precise mechanisms through which PSMB9 contributes to the initiation, progression, and immune regulation of colorectal cancer remain unclear. This study aims to investigate the expression characteristics and biological functions of PSMB9 in colorectal cancer, and to further elucidate the molecular pathways underlying its role in colorectal cancer initiation and progression. The findings are expected to provide a theoretical… More >

  • Open Access

    ARTICLE

    Multi-Omics Identification of UBE2C as a Prognostic Biomarker and Therapeutic Target Linked to Topotecan Sensitivity in Cervical Cancer

    Emmanuel Naveen Raj1,#, Chia-Jung Li1,2,3,4,5,#, Shih-Hsuan Cheng1, Su-Boon Yong6,7, Zhi-Hong Wen3,8, An-Jen Chiang1,9,*
    Oncology Research, DOI:10.32604/or.2026.079551
    (This article belongs to the Special Issue: Precision Oncology: Targeted Therapies and Tumor Microenvironment)
    Abstract Objectives: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) necessitate the discovery of novel biomarkers for prognostic and therapeutic advancement. This study aims to evaluate the clinical significance of ubiquitin-conjugating enzyme E2C (UBE2C) and its association with the tumor microenvironment (TME) in CESC. Methods: We meticulously sourced CESC data from renowned repositories such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO), leveraging cutting-edge techniques including single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and pharmacogenomics. Through multifaceted data analysis, we endeavored to unravel the intricate role and potential value of UBE2C in… More >
    Graphic Abstract

    Multi-Omics Identification of UBE2C as a Prognostic Biomarker and Therapeutic Target Linked to Topotecan Sensitivity in Cervical Cancer

  • Open Access

    REVIEW

    The Role of Mitochondrial ROS in Neoplastic Transformations, Progression and Therapeutic Targeting

    Bharath Kumar Velmurugan1, Shu Hui Lin2,3,4, Chih-Yang Huang5,6,7,8,9,10, Ming-Ju Hsieh9,11,12,*, Rathinasamy Baskaran10,*
    Oncology Research, DOI:10.32604/or.2026.083159
    Abstract Mitochondria are central regulators of cellular metabolism and survival and play a pivotal role in cancer development and progression through the production of reactive oxygen species (ROS), control of calcium homeostasis, regulation of autophagy, and modulation of cell death pathways. Mitochondria-derived ROS (mtROS) act as signaling mediators that influence tumor initiation, proliferation, metabolic reprogramming, metastasis, and therapeutic resistance by altering redox homeostasis, damaging mitochondrial DNA, and reshaping the tumor microenvironment. In addition to meeting the bioenergetic and biosynthetic requirements of rapidly proliferating cancer cells, mitochondrial metabolism modulates immune responses and supports cancer cell adaptation to More >

  • Open Access

    REVIEW

    The Emerging Role of microRNAs in Glioblastoma: From Liquid Biopsy to Nanotechnological Targeted Therapies

    Attilio Della Torre1,#,*, Andrea Filardo1,#, Isabella Coscarella1, Jessica Bria1, Anna Di Vito2, Emanuela Chiarella1, Adele Giovinazzo1, Emanuela Procopio1, Mariateresa Egiziano1, Riccardo Cassano1, Domenico La Torre3, Angelo Lavano1
    Oncology Research, DOI:10.32604/or.2026.084511
    Abstract Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor, characterized by a highly dismal prognosis and significant clinical challenges. Currently, assessing treatment success and monitoring tumor response relies heavily on neuroimaging. However, treatment modalities can temporarily alter imaging properties, leading to phenomena such as pseudoprogression, which confounds accurate disease evaluation. Furthermore, traditional tissue biopsies carry non-negligible neurological risks and are highly impractical for the longitudinal monitoring required to appreciate clonal evolution, identify acquired therapeutic resistance, or distinguish true recurrence. Consequently, there is an urgent clinical need for reliable, non-invasive diagnostic strategies. microRNAs (miRNAs),… More >

  • Open Access

    REVIEW

    Nuclear–Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance

    Xueping Zhu1,2,3,#, Misi He1,2,3,#, Ling Wang1,2,3,#, Rui Su4, Lin Zhong1,2,3, Ting Guo1,2,3,4, Haixia Wang1,2,3,*, Dongling Zou1,2,3,*
    Oncology Research, DOI:10.32604/or.2026.083902
    (This article belongs to the Special Issue: Molecular Targeting Therapy for Anticancer Treatment)
    Abstract Nucleocytoplasmic transport (NCT) regulates the spatial distribution of proteins and RNA between the nucleus and cytoplasm. NCT dysregulation can mislocalize tumor suppressors, DNA-repair factors, transcription factors, and drug targets in cancer. In this review, we conceptualize NCT-dependent protein mislocalization as a spatial regulatory framework for anticancer drug resistance, rather than as a catalogue of transport components. We systematically discuss how nuclear pore complex (NPC) remodeling, transport-receptor imbalance, post-translational modification (PTM)-regulated cargo routing, signaling-NCT crosstalk, nuclear localization signal/nuclear export signal (NLS/NES) alterations, and tumor microenvironmental pressures jointly drive aberrant nucleocytoplasmic distribution. These processes can further regulate… More >

  • Open Access

    REVIEW

    Cancer Stem Cell Biology: DNA Repair Mechanisms, Therapeutic Resistance, and Emerging Treatment Strategies

    Mateusz Kciuk1,2,*, Julia Gałęziewska2,3, Weronika Kruczkowska2,3, Katarzyna Wanke1,4, Damian Kołat1,2, Beata Marciniak1, Renata Kontek1
    Oncology Research, DOI:10.32604/or.2026.083197
    (This article belongs to the Special Issue: Targeting DNA Repair in Cancer)
    Abstract DNA is continuously challenged by endogenous and exogenous insults, generating lesions that threaten genomic stability. Normal stem cells preserve genome integrity through highly coordinated DNA damage response (DDR) networks involving efficient base excision repair (BER), homologous recombination (HR), cell-cycle checkpoints, and TP53-mediated quality control. Cancer stem cells (CSCs), a rare tumor subpopulation responsible for tumor initiation, metastasis, relapse, and therapeutic resistance, exploit these protective mechanisms while acquiring distinct DNA repair adaptations. This review examines how stemness-associated signaling pathways, including Hedgehog, Notch, and Wnt/β-catenin, interact with DDR programs to promote CSC survival under genotoxic stress. CSCs… More >

  • Open Access

    ARTICLE

    Impact of IL31RA Genetic Variants and Expression on Metastatic Progression in Oral Cavity Squamous Cell Carcinoma

    Hsueh-Ju Lu1,2,*, Chiao-Wen Lin3,4, Chun-Yi Chuang2,5, Chun-Wen Su6,7, Shun-Fa Yang6,7,*
    Oncology Research, DOI:10.32604/or.2026.080527
    Abstract Background: Interleukin-31 receptor alpha (IL31RA) has been implicated in cancer progression and tumor cell migration, but its genetic associations across cancers remain unclear. This study aimed to examine IL31RA polymorphisms in relation to lymph node involvement in oral cavity squamous cell carcinoma (OCSCC). Methods: In this case-control study, 2845 participants were enrolled, including 1352 patients with OCSCC and 1493 cancer-free controls. Associations between IL31RA SNPs and OCSCC susceptibility and clinicopathological characteristics were evaluated. Functional analyses, including cell migration assays, together with bioinformatic database analyses, were performed to investigate the biological significance of IL31RA and genotype–expression correlations. Logistic… More >

  • Open Access

    REVIEW

    Oral DNA Demethylating Agents and Epigenetic Targeting in Adult T-Cell Leukemia/Lymphoma

    Yuta Yamamoto1,2, Hiroshi Ureshino1,2,*, Shinya Kimura1,2
    Oncology Research, DOI:10.32604/or.2026.084740
    (This article belongs to the Special Issue: Molecular Targeting Therapy for Anticancer Treatment)
    Abstract DNA methylation plays a critical role in gene regulation and is frequently dysregulated in hematological malignancies such as myelodysplastic syndromes and acute myeloid leukemia. DNA demethylating agents have therefore emerged as important therapeutic options. However, conventional DNA demethylating agents require parenteral administration, which limits their long-term use and patient convenience. In this review, we aim to provide an overview of recent advances in the development of orally available DNA demethylating agents and discuss their therapeutic applications in hematological malignancies. Orally available DNA demethylating agents, such as CC-486 (oral azacitidine) and ASTX727 (a fixed-dose combination of More >

  • Open Access

    ARTICLE

    Efficacy and Safety of Durvalumab plus Tremelimumab for Unresectable Hepatocellular Carcinoma: A Real-World Multicenter Observational Study

    Krittiya Korphaisarn1,#,*, Kosin Wirasorn2,#, Suebpong Tanasanvimon3, Kijjakom Thanasombunsukh4, Kunlatida Maneenil5, Jirawat Thanestada6, Nattaya Teeyapun3, Jarin Chindaprasirt2, Chirawadee Sathitruangsak7, Teerada Siripoon8, Phannin Tiraswasdichai9, Chanchai Charonpongsuntorn10, Passakorn Wanchaijiraboon11, Wannisa Laosuangkoon12, Patrapim Sunpaweravong7, Ekapop Sirachainan8, Charuwan Akewanlop1
    Oncology Research, DOI:10.32604/or.2026.083206
    (This article belongs to the Special Issue: Advances in Liver Cancer: Novel Therapeutics and Biomarkers for HCC and CCA)
    Abstract Introduction: Durvalumab plus tremelimumab (Durva/Treme) improved survival in the HIMALAYA trial for unresectable hepatocellular carcinoma (HCC), but real-world evidence remains limited. This study aimed to evaluate clinical outcomes of Durva/Treme in routine practice. Methods: This retrospective multicenter study included patients with unresectable or advanced HCC who received Durva/Treme through the Expanded Access Program in Thailand between August 2023 and November 2025. Treatment outcomes and adverse events (AEs) were analyzed and descriptively compared with the HIMALAYA trial. Results: Fifty patients were included; median age was 62 years and 80% were male. Etiologies included hepatitis B (44%), hepatitis C… More >

  • Open Access

    REVIEW

    Metastatic Triple Negative Breast Cancer: Navigating a Rapidly Evolving Therapeutic Landscape

    Iseult M. Browne1,2, Monica Esteban Garcia1,2, Alicia F. C. Okines1,2,*
    Oncology Research, DOI:10.32604/or.2026.082829
    Abstract Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor, and HER2 expression, and carries a disproportionate burden of breast cancer-related mortality due to its aggressive biology and historically limited therapeutic options. The treatment landscape of metastatic TNBC has undergone a fundamental transformation over the past decade, driven by immune checkpoint inhibitors, antibody-drug conjugates (ADCs), and the identification of actionable genomic alterations. This review provides a comprehensive, clinically oriented appraisal of the current and emerging therapeutic landscape of metastatic TNBC, encompassing its molecular underpinnings and tumour microenvironment biology. We critically More >

  • Open Access

    REVIEW

    Cellular Immunotherapy for Cervical Cancer: Next Therapeutics Frontiers

    Danning Zhao, Qin Liu*
    Oncology Research, DOI:10.32604/or.2026.084736
    (This article belongs to the Special Issue: Advancing Cellular Therapeutics in Oncology: Innovations, Challenges, and Clinical Translation)
    Abstract Cervical cancer, particularly its advanced stages, requires novel therapeutic paradigms. Cellular immunotherapy exploits the constitutive expression of HPV E6/E7 oncoproteins as near-ideal tumor-specific antigens. This review systematically evaluates four principal platforms under investigation: tumor-infiltrating lymphocytes (TILs), TCR-engineered T cells, CAR-T cells, and CAR-NK cells. We critically analyze the preclinical rationale, clinical trial landscape, safety considerations, and manufacturing challenges for each modality. TIL therapy has achieved durable complete responses and an FDA Breakthrough Therapy designation. TCR-T cells enable precise targeting of intracellular viral epitopes but are HLA-restricted. CAR-T cells offer potent, MHC-independent recognition, yet face on-target/off-tumor More >

  • Open Access

    REVIEW

    Overcoming the Shield: Mechanisms of Resistance to DNA Repair Inhibitors and Strategies to Restore Synthetic Lethality

    Kannan Sridharan1, Ondrej Fiala2,3,4, Gowri Sivaramakrishnan5, Mimma Rizzo6, Matteo Santoni4,7,*
    Oncology Research, DOI:10.32604/or.2026.081879
    (This article belongs to the Special Issue: Targeting DNA Repair in Cancer)
    Abstract The emergence of resistance to poly (ADP-ribose) polymerase (PARP) inhibitors poses a significant obstacle in treating cancers characterized by BReast CAncer gene (BRCA) mutations or homologous recombination deficiency. Despite the substantial clinical benefits brought by drugs such as olaparib, niraparib, and talazoparib, a substantial proportion of tumors ultimately develop resistance. The underlying mechanisms are diverse and include the reconstitution of homologous recombination via secondary BRCA reversion mutations, stabilization of replication forks, enhanced drug efflux mediated by p-glycoproteins, and structural or functional alterations in PARP1 itself. A thorough grasp of these resistance pathways is critical for the… More >

  • Open Access

    REVIEW

    Immunotherapy in Advanced Epithelial Ovarian Cancer: Successes and Frustrations

    Lila A. Marshall*, Natalie L. Ayoub, Jill Tseng, Alex A. Francoeur
    Oncology Research, DOI:10.32604/or.2026.080161
    (This article belongs to the Special Issue: Recent Advances in Ovarian and Endometrial Cancers: Molecular Mechanisms and Targeted Therapies)
    Abstract Epithelial ovarian cancer (EOC) is most commonly diagnosed at an advanced stage and is known to recur frequently. Recurrent EOC can be difficult to treat, with limited effective options for systemic therapy. Platinum-resistant and -refractory recurrences are particularly difficult to treat, with even fewer therapeutic options than for platinum-sensitive recurrences. Less common histologic subtypes are also challenging, often with poor responses to typical systemic therapies and limited clinical trial data. With successes in the use of immunotherapy (IO) in other types of solid tumors, IO has been investigated extensively in EOC. However, the incorporation of… More >

  • Open Access

    REVIEW

    Regulation of the Wnt/β-Catenin Signaling Pathway by Non-Coding RNAs in Esophageal Squamous Cell Carcinoma: Mechanisms, Translational Relevance, and Therapeutic Implications

    Chao Han, Ming Hou, Ruifeng Yang, Xiaoping Wei, Cheng Wang*
    Oncology Research, DOI:10.32604/or.2026.081222
    Abstract Esophageal Squamous Cell Carcinoma (ESCC) is a highly aggressive malignancy characterized by a poor long-term prognosis. Aberrant activation of the canonical Wnt/β-catenin pathway serves as a central oncogenic driver in ESCC, with large-scale genomic analyses revealing that most patients harbor alterations in pathway-associated genes. This signaling axis orchestrates a wide array of malignant phenotypes, including tumor proliferation, invasion, epithelial-mesenchymal transition (EMT), cancer stemness, and therapeutic resistance. Therefore, this review aims to provide a comprehensive synthesis of the multifaceted crosstalk between various ncRNA classes and the Wnt/β-catenin axis, highlighting their roles in ESCC progression and their… More >

  • Open Access

    REVIEW

    Stage-Specific Regulation of Ubiquitination Modifications and Prospects for Targeted Therapy in Triple-Negative Breast Cancer

    Yongpan Wang1,#, Weiqiang Huang1,#, Qizhuan Lin2, Helei Cai2, Fengjin Dai3, Haiqing Gu1, Shunyan Yu1, Libo Jin2,*, Renyi Peng2,*
    Oncology Research, DOI:10.32604/or.2026.080113
    (This article belongs to the Special Issue: Advances in Pathology, Early Diagnosis and Therapeutic Strategies for Breast Cancer)
    Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor clinical outcomes. Owing to the absence of estrogen receptors, progesterone receptors, and Human Epidermal Growth Factor Receptor 2 (HER2) expression, TNBC shows limited responsiveness to conventional endocrine and targeted therapies. This subtype exhibits strong heterogeneity, a high propensity for metastasis, and a tendency to develop acquired drug resistance. Its survival and progression largely rely on non-classical signaling pathways, including Epidermal growth factor receptor (EGFR), Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), and Notch, which collectively impose substantial challenges to clinical management. In recent… More >

  • Open Access

    REVIEW

    Targeting the Neuro-Immune Axis in Next-Generation Oncology: Discovery and Validation of β2-Adrenergic Blockade to Reverse Ecosystem-Wide Resistance

    Heng Xu1,#, Jiaan Lu1,#, Zizhang Wang1,#, Jiayu Xu2, Shihui Peng3, Haiqing Chen4, Qiang Cao5,*, Qing Sun6,*, Shangke Huang7,*
    Oncology Research, DOI:10.32604/or.2026.083919
    (This article belongs to the Special Issue: Next-Generation Oncology: Unearthing and Validating Novel Therapeutic Targets)
    Abstract Despite the potential of current cancer immunotherapies, tumor cells frequently evade immune surveillance by forming an immunosuppressive microenvironment, leading to treatment resistance. Current inquiry positions the sympathetic nervous system (SNS) at the forefront of tumor immunology as a critical driver of this immune evasion. This review delineates the cellular pharmacology of SNS-mediated immune regulation across the tumor ecosystem. Operating predominantly through the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling axis, the SNS engages in bidirectional regulation with immune cells of the tumor microenvironment (TME). Norepinephrine and epinephrine interact with β2-adrenergic receptors (β2-ARs), triggering G-protein dissociation, adenylyl… More >

  • Open Access

    REVIEW

    Advances in the Research and Development of Breast Cancer Organoids

    Ling Li1,2,#, Shuai Zhao3,#, Xiaoxiao Wang2, Jiahui Du2, Zhen Jin1, Song-Bai Liu1,2,*, Xiaohua Li2,3,*
    Oncology Research, DOI:10.32604/or.2026.083636
    (This article belongs to the Special Issue: Breaking the Bottleneck of Therapeutic Resistance in Solid Tumors: Emerging Technologies, Novel Targets, and Innovative Strategies)
    Abstract Breast cancer ranks first in global cancer incidence. Due to its high heterogeneity, cancer cells often develop drug resistance during metastasis, leading to therapeutic challenges and poor prognosis. Consequently, breast cancer organoid models have emerged, which can effectively recapitulate the tumor microenvironment and serve as important tools for investigating the mechanisms underlying breast cancer initiation and progression. Breast cancer organoids exhibit interactions between cells and the extracellular matrix (ECM) while retaining the heterogeneity of the original tumor cells. Owing to these advantages, such models have been widely applied in studies of tumor pathogenesis, disease modeling,… More >

  • Open Access

    REVIEW

    Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies

    Jie Wu1,2, Zhewei Zhang1,2, Kit Ying Chan1,2, Tat San Lau1,2,*, Chi Chiu Wang1,2,3,*
    Oncology Research, DOI:10.32604/or.2026.083359
    (This article belongs to the Special Issue: Targeting the Tumor Microenvironment: Emerging Insights into Cancer Progression and Therapeutics)
    Abstract Ovarian cancer is the most lethal gynecological malignancy, with most patients diagnosed at an advanced stage and eventually relapsed after post-platinum-taxane chemotherapy. High intratumoral heterogeneity, extensive peritoneal dissemination, and acquired chemoresistance continue to restrict the clinical benefits of current therapeutic strategies. Increasing evidence indicates that ovarian cancer stem cells (OCSCs), a rare but highly plastic subpopulation characterized by self-renewal, multilineage differentiation, quiescence, tumor-initiating capacity, and intrinsic stress tolerance, play pivotal roles in tumor initiation, metastasis, recurrence, and therapeutic resistance. In this review, we systematically summarize current knowledge regarding the identification and functional characterization of OCSCs More >

  • Open Access

    REVIEW

    Targeting ATM Kinase in Cancer—A Comprehensive Review

    Mateusz Kciuk1,2,*, Gabriela Machura3,4, Katarzyna Wanke1,5, Piotr Gromek2,6, Beata Marciniak1, Renata Kontek1
    Oncology Research, DOI:10.32604/or.2026.082180
    Abstract Ataxia–telangiectasia mutated (ATM) is a central regulator of the DNA damage response (DDR), coordinating DNA double-strand break signaling, checkpoint activation, and maintenance of genome stability. Although traditionally regarded as a tumor suppressor, accumulating evidence indicates that many established cancers become functionally dependent on residual ATM signaling to tolerate oncogene-driven replication stress, genomic instability, oxidative stress, and defective checkpoint control. This context-dependent reliance reflects a form of non-oncogene addiction in which ATM signaling is selectively retained to sustain tumor cell survival, particularly in TP53-deficient and highly replication-stressed malignancies. Beyond canonical DDR functions, ATM also contributes to tumor… More >

  • Open Access

    ARTICLE

    Combinatorial Effects of Plasma-Treated Solution and Plasma-Treated Hydrogel with Cisplatin in Vulvar Cancer Cells

    Estelle C. I. D. Schad1,#, Janet P. Raja Xavier1,#, Hortense Decool1, Marcel Arnholdt1, Franziska Keßler1, Jan Schöttke1, Sara Y. Brucker1, Ernst Oberlechner1, Johanna Laupp1, Martin Weiss1,2,*
    Oncology Research, DOI:10.32604/or.2026.081755
    (This article belongs to the Special Issue: Advances in Cancer Therapeutics)
    Abstract Background: Vulvar squamous cell carcinoma (VSCC) is a rare, but increasingly prevalent malignancy with limited therapeutic options in the advanced disease state. Cisplatin-based chemoradiation remains the standard of care but is constrained by cumulative toxicity. Precancerous lesions, including high-grade squamous intraepithelial lesions (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN), similarly require effective yet tolerable treatments. Low-thermal Argon plasma devitalization (ltAPD), a source of reactive oxygen and nitrogen species (RONS), has emerged as a promising approach for redox-based tumor modulation. This study aimed to evaluate the anti-tumor efficacy of two plasma modalities, plasma-treated solution (PTS) and plasma-treated… More >

  • Open Access

    REVIEW

    The Double-Edged Sword of Genomic DNA Methylation: Orchestrating Gastric Carcinogenesis and Shaping Precision Oncology

    Xuan Chen, Chao Luo, Wei Wen*
    Oncology Research, DOI:10.32604/or.2026.079753
    Abstract This article systematically elaborates on the dual role of DNA methylation in the initiation and progression of gastric cancer and its potential clinical applications in precision oncology. As a core epigenetic mechanism, DNA methylation drives the multistage development of gastric cancer through the coordinated dysregulation of genome-wide hypomethylation and promoter-specific hypermethylation, playing a key role in chronic inflammation and epigenetic reprogramming, particularly in the context of Helicobacter pylori infection. The article focuses on analyzing the central pathogenic mechanisms of DNA methylation, including the silencing of tumor suppressor genes, induction of genomic instability, promotion of the CpG More >

  • Open Access

    REVIEW

    Hexokinases and Glial Tumor Metabolism: A Bridge between Bioenergetics and Translational Oncology

    Corina Ionela Tamas1,2, Flaviu Tamas1,2,*, Alina Roxana Cehan3, Adrian Balasa1,2
    Oncology Research, DOI:10.32604/or.2026.079467
    Abstract Hexokinases, particularly hexokinase 2, play a central role in the metabolic reprogramming of glioblastoma and other malignant glial tumors by promoting aerobic glycolysis and sustaining the Warburg phenotype. This review aims to summarize the current evidence regarding the molecular regulation, biological significance, and therapeutic implications of hexokinase isoenzymes in glial tumor metabolism. Recent studies consistently demonstrate that hexokinase 2 overexpression is associated with enhanced tumor proliferation, invasiveness, angiogenesis, resistance to chemotherapy and radiotherapy, and poor prognosis, especially in glioblastoma and high-grade gliomas. Multiple regulatory mechanisms, including microRNAs, long non-coding RNAs, the phosphatidylinositol 3-kinase/protein kinase B More >

  • Open Access

    REVIEW

    Toxicities of Fruquintinib in Gastrointestinal Malignancies: A Systematic Review and Meta-Analysis

    Daniel Thomas Jones1,*, Tajveer Sangha1, Arman Manjikian1, Micheal Ghobrial1, Qasim Shawesh1, Emaan Tiwana1, Emi Hearn1, Arash Latif1, Elaine Tupas1, Aishwarya Hanspal1, Rishi Kumar Nanda2, Ramaditya Srinivasmurthy3, Jason Ta4, Meghana Pandit3, Charles Abraham Joseph Larson5, Kyaw Zin Thein6
    Oncology Research, DOI:10.32604/or.2026.078524
    Abstract Backgrounds: Fruquintinib is a selective vascular endothelial growth factor receptor (VEGFR)-1/2/3 inhibitor approved for previously treated metastatic colorectal cancer. As its use expands across gastrointestinal (GI) malignancies and combination regimens, randomized evidence is needed to define the toxicity profile most relevant to clinical monitoring, particularly hypertension, dermatologic toxicity, renal toxicity, bleeding, and thrombotic events. The objective of this study was to synthesize randomized controlled trial evidence to quantify the incidence and relative risk of key toxicities associated with fruquintinib in gastrointestinal malignancies. Methods: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception through 1 January 2026… More >

  • Open Access

    REVIEW

    Immunotherapy in Bellini Duct Carcinoma: A Systematic Review

    Antonio David Lázaro-Sánchez1,2,*, Javier David Benítez-Fuentes3, Sofía Wikström-Fernández4, María Nevado-Rodríguez5, Pablo Conesa-Zamora2,6, Ginés Luengo-Gil2,6, Alejandra Ivars-Rubio5, Marta Zafra-Poves5, Edgardo D. Carosella7, Belén Fernández-Molina8, Andrés Nieto-Olivares9, María José Sánchez de las Matas Garre10, Ana Belén Arroyo2,6
    Oncology Research, DOI:10.32604/or.2026.081674
    (This article belongs to the Special Issue: Advances in Cancer Immunotherapy)
    Abstract Background: Collecting duct carcinoma (CDC; Bellini duct carcinoma) is a rare, aggressive renal cancer with no established standard of care, and evidence for immune checkpoint inhibitor (ICI)-based therapy in CDC remains emerging and fragmented. We aimed to systematically synthesise efficacy and safety data on immunotherapy in adult patients with CDC. Methods: PubMed and Web of Science were searched from inception to 29 March 2025, with targeted post-search monitoring of key journals and ClinicalTrials.gov updated on 11 April 2026. Prospective interventional studies, observational cohorts/registries, and case series/reports were eligible. Screening, extraction and risk-of-bias appraisal (Joanna Briggs Institute… More >

  • Open Access

    REVIEW

    Nanorobots and Exosomes: Driving the New Frontier for Bladder Tumors through Non-Coding RNAs

    Lorenzo Spirito1, Cristina Quintavalle2, Paola Coppola1, Matteo Esposito3, Francesco Esposito2,3, Gabriella De Vita3, Pierlorenzo Pallante2,3,*
    Oncology Research, DOI:10.32604/or.2026.078045
    (This article belongs to the Special Issue: Innovations in Genitourinary Oncology: Integrating Tumor Immunology and Precision Medicine)
    Abstract Because of its limited treatment choices and high recurrence rates, bladder cancer (BCa) presents a significant clinical issue. As a result, current research is concentrated on creating novel approaches for early diagnosis and more specialized treatments. Nanorobots hold significant potential as precise medicine-delivery systems and as in situ diagnostic vectors within this dynamic environment. Personalized treatments are becoming increasingly feasible thanks to new insights into the molecular pathways driving tumor growth, revealed through studies on exosomes and non-coding RNAs (ncRNAs), however, their true potential lies in integrating these findings. This review analyzes the role of nanorobots,… More >

  • Open Access

    REVIEW

    Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies

    Agata Kosmaczewska*, Lidia Ciszak
    Oncology Research, DOI:10.32604/or.2026.081365
    Abstract Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous B cell malignancy in which non-malignant T lymphocytes constitute a critical component of the tumor microenvironment and significantly influence disease evolution and the therapeutic response. Growing evidence suggests that CLL-associated T cells not only participate in the antitumor response but also activate signals that promote the development of CLL subclones. Although novel targeted therapies, such as Bruton’s tyrosine kinase (BTK) inhibitors, BTK degraders, B-cell lymphoma 2 (BCL-2) inhibitors, T cell engagers, immune checkpoint inhibitors, and adoptive T cell therapy have different mechanisms of action, they affect the More >

  • Open Access

    REVIEW

    Current Insights into the Role of Peripheral Blood Immune Cell Phenotypes in Resistance to Cancer Therapies

    Allinson Olaechea1,2, Cristina Camacho Rubio2, Sara Gómez-Melero3,4,*
    Oncology Research, DOI:10.32604/or.2026.079865
    (This article belongs to the Special Issue: Deciphering Mechanisms of Cancer Therapy Resistance: In Vitro Models to Study Drug Resistance and Radiation-Drug Responses in Cancer and Normal Cells)
    Abstract Peripheral blood mononuclear cell (PBMC) immunophenotyping has emerged as a promising non-invasive approach to characterize systemic immune alterations in cancer and to identify biomarkers associated with treatment response and resistance. However, current evidence remains fragmented and predominantly descriptive, with substantial heterogeneity in study design, immunophenotyping methodologies, and patient populations, limiting the identification of robust and clinically translatable immune signatures. In this review, we aim to comprehensively analyze PBMC immune phenotypes across multiple cancer types, with particular emphasis on their association with disease progression, therapeutic outcomes, and the key methodological and translational challenges that currently limit… More >

  • Open Access

    ARTICLE

    On-Treatment Grade 3–4 Neutropenia and Clinical Outcomes with Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: ReTrITA Real-World Evidence

    Carlo Signorelli1,*, Michele Basso2, Annunziato Anghelone2, Maria Alessandra Calegari2, Alessandro Passardi3, Chiara Gallio3, Alessandro Bittoni3, Jessica Lucchetti4, Lorenzo Angotti4, Emanuela Di Giacomo4, Ina Valeria Zurlo5, Cristina Morelli6, Emanuela Dell’Aquila7, Adele Artemi7, Donatello Gemma8, Domenico Cristiano Corsi9, Alessandra Emiliani9, Marta Ribelli9, Federica Mazzuca10, Giulia Arrivi10, Federica Zoratto11, Maria Grazia Morandi12, Fiorenza Santamaria13,14, Manuela Dettori15, Antonella Cosimati16, Rosa Saltarelli17, Alessandro Minelli18, Emanuela Lucci-Cordisco19, Mario Giovanni Chilelli1
    Oncology Research, DOI:10.32604/or.2026.080964
    (This article belongs to the Special Issue: Precision Beyond Progression: Real-World Evidence and Dynamic Prognostic Markers in Refractory Metastatic Colorectal Cancer)
    Abstract Background: Trifluridine/tipiracil (T) is a standard treatment for refractory metastatic colorectal cancer (mCRC). In randomized trials, treatment-emergent neutropenia has been associated with improved outcomes, suggesting a potential link with drug activity. However, evidence from routine clinical practice remains limited. This sub-analysis of the multicenter ReTrITA study evaluated the association between severe neutropenia and clinical outcomes in a real-world setting. Methods: Patients with refractory mCRC treated with T within the ReTrITA cohort were included. Patients were stratified according to the occurrence of grade 3–4 neutropenia. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier… More >

  • Open Access

    REVIEW

    Resistance Mechanisms in Immunotherapy-Radiotherapy/Chemotherapy Combinations in Locally Advanced Head & Neck Squamous Cell Carcinoma

    Abbas Hussain1,*, Daniel Thomas Jones2, Rishi Kumar Nanda3, Ramaditya Srinivasmurthy4, Jason Ta5, Yin Mon Myat6, Riccesha Hattin1, Jo-Lawrence Bigcas7, Sisi Tian7, Suparna Shah7, Robert Wang7, Kyaw Zin Thein8
    Oncology Research, DOI:10.32604/or.2026.077918
    (This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)
    Abstract Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains difficult to treat despite multimodal therapy. Immune checkpoint inhibitors (ICIs) have expanded treatment options, but phase III trials combining ICIs with chemoradiotherapy have demonstrated limited survival benefit due to complex resistance mechanisms. These include immunosuppressive tumor microenvironments, impaired DNA damage responses, hypoxia-driven adaptations, metabolic reprogramming, and oncogenic signaling via the HER receptor family. This review outlines key resistance pathways and emerging strategies to overcome them. Nanotechnology-based approaches may enhance drug delivery and modulate the tumor microenvironment, while dual inhibition of epidermal growth factor receptor (EGFR), More >

  • Open Access

    REVIEW

    Cholesterol Metabolism in Cancer Patients: Mechanisms, Treatment-Related Effects, and Cardio-Oncology Management

    Mariagrazia Piscione1,*, Barbara Pala2,3,*, Francesco Cribari3, Paola Gualtieri4, Dario Gaudio5, Marco Alfonso Perrone6, Laura Di Renzo4
    Oncology Research, DOI:10.32604/or.2026.079215
    (This article belongs to the Special Issue: Metabolic and Inflammatory Dysregulation as Therapeutic Targets in Cancer)
    Abstract Cholesterol metabolism is central to cancer biology, influencing tumour initiation, progression, and therapeutic response, while contributing to the increased cardiovascular risk observed in cancer patients. Epidemiological studies investigating the relationship between circulating cholesterol levels and cancer risk have yielded conflicting results, reflecting substantial biological heterogeneity, tumour-specific metabolic demands, and methodological biases such as reverse causality. At the cellular level, malignant cells exhibit elevated cholesterol uptake and synthesis to sustain membrane biogenesis, lipid raft-dependent oncogenic signalling, and rapid proliferation. Cholesterol and its oxidized derivatives further modulate inflammation, angiogenesis, immune evasion, and key signalling pathways. Anticancer therapies… More >

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