Open Access
REVIEW
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
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
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
ARTICLE
Tingting Yang1, Meng Guan1, Xin Guan1, Lihua Kang1, Xiaomeng Wang1, Yanjie Guan1, Yang Yang2, Wei Deng3, Guoxiang Wang1,*
Oncology Research, DOI:10.32604/or.2026.083563
（This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))
Abstract Background: Tumor-driven vascular remodeling is crucial for breast cancer metastasis; yet, the role of tumor-derived exosomal miRNAs in this process remains underexplored. This study aimed to investigate the clinical relevance and the underlying mechanism of breast cancer-derived exosomal miR-92b-3p in endothelial reprogramming. Methods: miR-92b-3p expression was evaluated in the TCGA cohort and clinical patient samples. The effects of exosomal miR-92b-3p from breast cancer cells on recipient human microvascular endothelial cells (HMVECs) were assessed using in vitro angiogenesis, migration, and permeability assays, alongside in vivo murine xenograft models. Mechanistic targets were validated via dual-luciferase and rescue experiments. Results: miR-92b-3p was… More >
Open Access
ARTICLE
Beatrice Sani1,2, Alessandro Cignetti2, Marta Leporati3, Sara Sommariva4, Marco Armenio1, Valerio Tenace5, Arianna Savi2, Johanna Umurungi1,2, Giovanni Fornari1,2, Simone Busso3, Alessandra Canevaro3, Igor Bisognin3, Silvia Marini1, Michele Piana4, Daniela Cilloni1,2, Valentina Gaidano2,*
Oncology Research, DOI:10.32604/or.2026.078245
Abstract Objectives: Venetoclax (VEN) is approved for acute myeloid leukemia (AML) in association with azacitidine, in a 28-day schedule at a fixed dosage, which requires reduction if azoles are co-administered. The present study aims to evaluate VEN therapeutic drug monitoring (TDM) in a real-word setting, where the VEN schedule is frequently reduced, investigating: (i) the posaconazole impact, and (ii) whether VEN exposure correlates with safety and efficacy. Methods: We analyzed data from 43 AML patients treated with different VEN-containing regimens, for whom a near-trough VEN plasma concentration (Cmin) was determined at different timepoints (days 5-8-11-15-22-29) across different cycles… More >
Open Access
REVIEW
Giovanni Leuzzi1,*, Michele Ferrari1, Federica Sabia1, Alessandro Pardolesi1, Alessia Stanzi1, Claudia Proto2, Giuseppe Lo Russo2, Arsela Prelaj2, Monica Ganzinelli2, Matteo Calderoni1, Clarissa Uslenghi1, Ugo Pastorino3, Piergiorgio Solli1
Oncology Research, DOI:10.32604/or.2026.077158
（This article belongs to the Special Issue: Integrative Strategies in Cancer Therapy)
Abstract Backgrounds: Despite the availability of multimodal strategies, no universally accepted guidelines exist for the management of advanced Thymic Epithelial Tumors (TETs), particularly in locally advanced thymomas. The aim of this study was to evaluate the oncological and surgical outcomes of induction therapy (IT) followed by surgery in patients with Masaoka–Koga stage III–IVA TETs. To this end, we conducted a systematic review and meta-analysis assessing surgical-pathological and survival outcomes. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed.… More >
Graphic Abstract
Open Access
REVIEW
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
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
ARTICLE
Ching-Chun Ho1, Yen-Cheng Chen1,2, Wei-Liang Lean1, Wen-Sheng Wu1,*
Oncology Research, DOI:10.32604/or.2026.077693
（This article belongs to the Special Issue: Integrative Strategies in Cancer Therapy)
Abstract Objectives: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), as well as protein kinase B (AKT), are potential therapeutic targets for TNBC. Programmed death-ligand 1 (PD-L1) is implicated in TNBC progression and is associated with AKT and ERK signaling pathways. In addition, reactive oxygen species (ROS) act upstream of MAPK/AKT and PD-L1. In this study, we aimed to clarify the role of PD-L1 in TNBC progression and to delineate the underlying signaling mechanisms. Methods: Western blotting and reverse… More >
Open Access
REVIEW
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
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
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
ARTICLE
Hui Zhou1,2, Jiarui Wang3, Zhili Qiao4, Xin Liao1,*
Oncology Research, DOI:10.32604/or.2026.082613
（This article belongs to the Special Issue: Advances in Cancer Immunotherapy)
Abstract Objectives: Uncoupling protein 2 (UCP2) has been extensively studied as a metabolic regulator in glioma; however, its relationship with the tumour immune microenvironment and the cellular source of its expression within the glioma tumour microenvironment (TME) remains poorly understood. This study aimed to characterise UCP2 expression at single-cell resolution and evaluate its immunological significance in glioma. Methods: This study employed an integrative multi-omics approach incorporating bulk transcriptomics, scRNA-seq (GSE70630, GSE84465, and GSE89567; n = 13,216 cells), immune deconvolution, immunohistochemistry (n = 96 glioma patients), and immunofluorescence co-staining (n = 6). Results: Pan-cancer analysis confirmed UCP2… More >
Open Access
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
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
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
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
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
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
ARTICLE
Haijun Sun1,#, Wenyue Yan2,#, Zhanyu Li3,#, Qintian Li4, Qilong Du4, Li Xu5, Wanwei Cao3, Junrong Yang6, Xilan Yang2, Jun Chen7,*, Yuan Mao8,*, Wen Huang4,*
Oncology Research, DOI:10.32604/or.2026.080413
Abstract Background: The melanoma-associated antigen-A1 (MAGE-A1) demonstrates tumor-restricted expression patterns in diverse malignancies, positioning it as an attractive therapeutic target. This investigation aimed to engineer and validate a novel antibody-drug conjugate with oxaliplatin targeting MAGE-Al (MIg-OXA), a novel antibody-drug conjugate targeting MAGE-A1, while assessing its therapeutic potential against MAGE-A1-expressing lung adenocarcinoma through both cellular and animal models. Methods: We generated a MAGE-A1-specific immunoglobulin G (IgG) antibody (MIgG) and subsequently conjugated it with oxaliplatin (OXA) to produce MIgG-OXA. The conjugate’s binding specificity and cellular uptake were verified through cell-based enzyme-linked immunosorbent assay (ELISA), flow cytometric analysis, and immunofluorescence… More >
Open Access
ARTICLE
Wei Lee1, Hung-Yu Lin1,2,*, Pei-Yi Chu1,3,*
Oncology Research, DOI:10.32604/or.2026.078813
（This article belongs to the Special Issue: Tumor Biomarkers for Diagnosis, Prognosis and Targeted Therapy)
Abstract Background: Guanylate kinase 1 (GUK1) is crucial for nucleotide metabolism, yet its impact on breast cancer (BC) progression remains poorly defined. The objective of the present study is to investigate GUK1 as a prognostic biomarker and therapeutic target. Methods: We employed a multi-omics approach integrating The Cancer Genome Atlas (TCGA) data, machine learning algorithm, High-Definition spatial transcriptomics (Visium HD), single-cell profiling, molecular docking and experimental validation including in vitro knockdown models and Surface Plasmon Resonance (SPR). Results: LASSO regression identified GUK1 as a key metabolic driver. High expression correlated significantly with poor survival and was most pronounced in… More >
Open Access
REVIEW
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
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
ARTICLE
Lisa J. Frey1,*, Nina Lache1, Nikita D. Fischer1, Niklas Rölz1, Lisa Frey1, Maximilian Haack1, Gregor Duwe1, Stefan Porubsky2, Axel Haferkamp1, Daniel-C. Wagner2,3, Maximilian P. Brandt1
Oncology Research, DOI:10.32604/or.2026.078954
Abstract Objectives: Squamous cell carcinoma (SCC) of the bladder is an aggressive histologic subtype with distinct clinical behavior and limited treatment options after platinum-based chemotherapy. This study aimed to evaluate potential therapeutic targets in bladder SCC. Methods: A retrospective cohort of 790 patients who underwent radical cystectomy for bladder cancer between 2011 and 2021 was screened to identify cases with histologically confirmed SCC. All SCC cases in the pathology department from 2003 to 2011 were also reviewed. Clinical and pathological data from 54 patients were analyzed. A tissue microarray (TMA) was constructed, and immunohistochemical (IHC) analyses… More >
Open Access
ARTICLE
Yasmine Labiad1, Céline Baier1, Michèle Genin2, Caroline Besson3,4, Sophie Prevot5, Hubert Lepidi6, Régis Costello1,7,*
Oncology Research, DOI:10.32604/or.2026.076241
Abstract Objectives: Transcriptomic profiling has enabled the classification of Diffuse Large B-Cell Lymphoma (DLBCL) into distinct subtypes, such as Germinal Center B-cell-like (GCB) and Activated B-cell-like (ABC), primarily in HIV-negative patients. However, HIV-associated DLBCL may follow different molecular mechanisms due to immune dysregulation. This study aimed to characterize the transcriptomic landscape of HIV-related DLBCL to identify distinct subtypes and deregulated pathways with potential theranostic implications. Methods: Twelve formalin-fixed, paraffin-embedded DLBCL samples from HIV-positive patients were analyzed using Agilent’s microarray. Quantile normalization and unsupervised hierarchical clustering were performed to classify tumors based on gene expression profiles. Results: Two distinct More >
Graphic Abstract
Open Access
ARTICLE
Mao-Lin Chen1, I-Che Chung1, Kevin Chih-Yang Huang2,3,4,5, K. S. Clifford Chao6,7,8, Ta-Tung Yuan1,*
Oncology Research, DOI:10.32604/or.2026.077930
Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive and metabolically rewired tumor microenvironment (TME). Although α-enolase (ENO1) is frequently overexpressed in PDAC and associated with poor prognosis, its functional role in TME remodeling remains unclear. This study investigated the role of ENO1 in plasmin-dependent transforming growth factor β (TGFβ) activation and metabolic adaptation in PDAC and evaluated the therapeutic potential of HuL001, a first-in-class humanized anti-ENO1 monoclonal antibody. Methods: ENO1 expression and clinical relevance were evaluated in PDAC tissues by immunohistochemistry. Mechanistic studies were performed using PDAC-monocyte co-culture systems, reverse transcription-quantitative PCR (RT-qPCR), enzyme-linked… More >
Open Access
REVIEW
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
Bin Lan1, Jie Tan1, Qing Wang1, Siyuan Zeng2,*
Oncology Research, DOI:10.32604/or.2026.081711
（This article belongs to the Special Issue: Advancements in Hepatocellular Carcinoma Treatment)
Abstract Backgrounds: Cyclin-dependent kinase 7 (CDK7) plays key roles in transcription and cell cycle regulation, and its inhibition has been proposed as a potential therapeutic strategy for hepatocellular carcinoma (HCC). The primary research objective of this study is to identify and validate CDK7-associated prognostic genes in HCC using bioinformatics approaches, construct a reliable prognostic risk model, and explore the functional role of CDK7 in HCC progression through in vitro and in vivo experiments, with a specific focus on its association with RelA/p65 phosphorylation, so as to provide evidence supporting CDK7 as a potential prognostic biomarker and therapeutic target for… More >
Open Access
ARTICLE
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
ARTICLE
Yiming Ma1,2,#, Zhihan Zhang1,2,#, Hongli Pan3, Hailin Jiang1,2, Lili Guo4,*, Fengjie Guo1,2,*
Oncology Research, DOI:10.32604/or.2026.079515
（This article belongs to the Special Issue: Selected Papers from 2026 International Conference on New Models for Cancer Prevention and Treatment (NMCPT 2026))
Abstract Objectives: Lung adenocarcinoma (LUAD) has a poor prognosis, and effective metabolic biomarkers are still few. Glutamine metabolism is one of the central features of tumor metabolic reprogramming, but the cellular heterogeneity and clinical significance of glutamine metabolism in the LUAD tumor microenvironment (TME) remain unknown. The goal of this paper was to define glutamine metabolism on a single-cell basis and determine major regulators that have predictive value. Methods: A single-cell RNA sequencing dataset (GSE149655) was combined with The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus (GEO) datasets in order to evaluate the… More >
Open Access
ARTICLE
Jia Liu1,2,#, Binqian Wang1,#, Yannan Jin1, Wenquan Chen1, Ruohan Shi1, Weijia Wang1, Xiaojing Zhang1, Yi Tan3, Zhongran Man3, Bo Hu1, Lisen Zhu1, Biao Zhang3,*, Chongchan Bao4,5,*, Gongsheng Jin1,*
Oncology Research, DOI:10.32604/or.2026.079137
（This article belongs to the Special Issue: Next-Generation Oncology: Unearthing and Validating Novel Therapeutic Targets)
Abstract Backgrounds: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a unique tumor microenvironment, and while Programmed cell death protein 1/Programmed cell death ligand 1 (PD-1/PD-L1) blockade represents a standard immunotherapy, most patients develop primary or acquired resistance, with few alternative immunotherapeutic targets currently available. Therefore, we aimed to identify potential immune checkpoint-related molecules involved in TNBC-macrophage crosstalk, clarify the underlying molecular mechanism mediated by small extracellular vesicles (sEVs), and provide a theoretical basis for the future development of novel immunotherapeutic targets against TNBC. Methods: Single-cell RNA-sequencing (scRNA-seq) datasets for various breast cancer… More >
Open Access
REVIEW
Alejandro Valdés1,2, Jaime González-Montero1,3, Carlos Rojas1,3, Mauricio Burotto1,3,*
Oncology Research, DOI:10.32604/or.2026.077711
Abstract Immune checkpoint inhibitors (ICIs) combined with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have transformed the treatment landscape of advanced clear cell renal cell carcinoma (ccRCC). Current guidelines favour ICI plus VEGF-TKI (IO+TKI) combinations for favourable-risk disease (International Metastatic RCC Database Consortium [IMDC] score 0) based on improved objective response rates and progression-free survival. However, no IO+TKI combination has demonstrated a statistically significant overall survival (OS) benefit in this subgroup. A pooled analysis of four pivotal phase III trials (n = 839 favourable-risk patients) revealed no OS advantage for IO+TKI versus sunitinib monotherapy (hazard… More >
Graphic Abstract
Open Access
REVIEW
Ioannis Anestopoulos1,*, Sotiris Kyriakou1, Maria Deligiorgi2, Dimitrios T. Trafalis2, Sotiris Botaitis3, Rodrigo Franco4,5, Aglaia Pappa6, Mihalis I. Panayiotidis7,*
Oncology Research, DOI:10.32604/or.2026.072349
Abstract Despite the use of targeted and/or immune-based therapeutic approaches, mortality rates among melanoma patients are high, mainly due to drug-induced resistance mechanisms. In parallel, alterations of epigenetic mechanisms (e.g., deregulated patterns of DNA methylation, aberrant histone modifications and abnormal expression levels of non-coding RNAs [ncRNAs]) have been associated not only with the pathophysiology of melanoma but also with the resistance against various immunotherapeutic drugs. In this review article, we discuss the involvement of different types of epigenetic mechanisms in melanoma progression. In addition, we report on melanoma’s immune environment and immunosuppressive mechanisms while we highlight More >
Open Access
REVIEW
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
CASE REPORT
Xin Qian, Xian Deng, Rongjia Zhang, Xu Li, Dehui Qiao, Xiaodong Chen, Hui Yang*
Oncology Research, DOI:10.32604/or.2026.079674
Abstract Background: Poorly differentiated thyroid carcinoma (PDTC) is a rare, aggressive malignancy. Cardiac metastasis from PDTC is exceedingly uncommon. We report early cardiac metastasis occurring shortly after radical thyroidectomy to highlight atypical distant spread and management challenges. Case Description: A 62-year-old woman presented four months after thyroidectomy with progressive exertional dyspnoea, fatigue, productive cough, facial oedema, lip cyanosis, and dizziness. Postoperative pathology showed poorly differentiated thyroid carcinoma of the right lobe and isthmus (pT2N1bM0) with capsular and recurrent laryngeal nerve invasion. Transthoracic echocardiography revealed a right atrial mass that enlarged to 5.3 × 4.0 cm and extended toward… More >
Open Access
REVIEW
Zhihao Wei1,#, Jijie Cai1,#, Sifen Wang2,#, Yachen Li3, Libo Luo1, Jun Chen1, Fuyu Li1, Hongyu Nie1, Ke Gong4,*, Manbo Cai1,*
Oncology Research, DOI:10.32604/or.2026.079281
（This article belongs to the Special Issue: Advances in Cancer Therapeutics)
Abstract Breast cancer (BC) remains a leading cause of cancer-related mortality worldwide, and accumulating evidence suggests that tumor-associated microbiota may contribute to disease heterogeneity beyond host genetic and immune determinants. Advances in sequencing and multi-omics technologies have uncovered a reproducible intratumoral microbiome in BC, with distinct compositional patterns associated with molecular subtypes, clinicopathological features, and clinical outcomes. Alterations in specific microbial taxa have also been linked to tumor immune status, metastatic potential, and therapeutic sensitivity, underscoring their potential value in disease stratification and prognostic assessment. Although breast tissue represents a low-biomass environment, multiple studies employing stringent… More >
Open Access
REVIEW
Shijia Lu1,#, Yanmin Wang1,#, Han Zhang1, Mengjia Yan1, Mengdan Sang2, Jinle Wang1, Huaying Du3, Jinwen Sima3, Yiran Zhen2, Xue Yang2, Yutong Zhang1, Hongwei Zhou1,*
Oncology Research, DOI:10.32604/or.2026.079988
Abstract Proliferating Cell Nuclear Antigen (PCNA) is a core protein in DNA replication and repair. Its functional dysregulation drives tumorigenesis and therapeutic resistance, making it a critical anticancer target. However, the fundamental conflict between PCNA’s indispensable “guardian” function in normal cells and its hijacked “accomplice” role in cancer cells constitutes the central challenge for targeted intervention: how to eradicate tumors while avoiding severe toxicity to normal tissues. This review aims to systematically review the latest advances and translational dilemmas in the field of PCNA-targeted therapy. It outlines various intervention strategies, including small-molecule inhibitors, proteolysis-targeting chimeras, post-translational More >
Graphic Abstract
Open Access
REVIEW
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 >
Open Access
REVIEW
Yen-Dun Tony Tzeng1,2,#, Chen-Yueh Wen3,4,#, Su-Boon Yong5,6, Zhi-Hong Wen7,8, An-Jen Chiang9,*, Chia-Jung Li8,10,11,12,*
Oncology Research, DOI:10.32604/or.2026.078924
（This article belongs to the Special Issue: Tumor Biomarkers for Diagnosis, Prognosis and Targeted Therapy)
Abstract Breast cancer (BC) management has transitioned from histological classification to molecular subtyping, yet therapeutic resistance and intratumor heterogeneity remain critical clinical challenges. This review examines the emerging paradigm shift toward integrating mitochondrial metabolism into the precision medicine framework. We detail the complex mitonuclear crosstalk where nuclear genetic alterations, such as Breast Cancer 1 (BRCA1) deficiency and TP53 mutations, fundamentally reprogram mitochondrial bioenergetics. Specifically, the loss of BRCA1 function triggers a systemic NAD+ depletion trap through PARP1 hyperactivation, while oncogenic drivers like MYC coordinate with PGC1α to enhance mitochondrial biogenesis for metastatic survival. We evaluate the diagnostic potential of… More >
Graphic Abstract
Open Access
REVIEW
Yaqi Xu1, Jia Zhao2, Xiaowen Mao1,*
Oncology Research, DOI:10.32604/or.2026.079562
（This article belongs to the Special Issue: Targeting the Tumor Microenvironment: Emerging Insights into Cancer Progression and Therapeutics)
Abstract Extracellular vesicles (EVs) are actively secreted, membrane-enclosed nanoparticles that serve as pivotal mediators of intercellular communication. They function as key mediators of intercellular communication by transporting diverse biomolecules, including proteins, nucleic acids, and metabolites. Within the tumor microenvironment, EVs drive complex cellular crosstalk and critically regulate tumor progression by remodeling the extracellular matrix, conferring drug resistance, and reprogramming immune responses. Given their natural biocompatibility, tissue tropism, and ability to cross biological barriers, EVs have emerged as promising platforms for immunotherapy, tumor vaccines and targeted drug delivery system. Moreover, the rapid expansion of EV-based clinical trials… More >
Graphic Abstract
Open Access
REVIEW
Zixin Wan1,2,#, Jingdan Quan1,2,#, Yue Qiu1,2, Zhiwei Zhang1,2,*
Oncology Research, DOI:10.32604/or.2026.082561
（This article belongs to the Special Issue: Gastroenteropancreatic Tumors: From Basic Research to Therapeutic Approach)
Abstract Gastric cancer (GC) is one of the malignant tumors with high incidence and mortality worldwide. It has concealed early symptoms, poor prognosis for advanced patients, and limited efficacy of conventional treatments. Metabolic reprogramming is a core hallmark of cancer, among which amino acid metabolic reprogramming plays a critical regulatory role in the initiation and progression of GC. By linking intracellular energy supply, biosynthetic demands, and tumor microenvironment remodeling, it participates in immune escape, redox homeostasis maintenance, and therapeutic resistance. Dysregulation of key amino acids, including arginine, tryptophan, glutamine, branched-chain amino acids, serine/glycine, and aspartic acid,… More >
Open Access
REVIEW
Cristian Cojocaru, Marcel Costuleanu*, Ovidiu Rusalim Petriș, Ruxandra Cojocaru, Decebal Vasîncu, Elena Cojocaru
Oncology Research, DOI:10.32604/or.2026.080024
Abstract Lung cancer in individuals who have never smoked (LCINS) represents a clinically and biologically distinct subset of non–small cell lung cancer, driven predominantly by oncogenic alterations rather than tobacco-related mutagenesis. This review aims to summarize current and emerging targeted and immune-based therapeutic strategies in LCINS individuals. These patients present a molecular profile that differs substantially from tobacco-associated disease and has direct consequences for treatment selection. Evidence published over the past five years has clarified how these molecular features shape treatment response and resistance in this setting. Particular attention is given to tumors with alterations in… More >
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