Chunwei Huang, Jingyi Kong, Hangxing Ren, Wanchen Zhang, Shi Jiang^*, Xianneng Sheng^*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.085387 - 16 July 2026

Abstract HER2-positive breast cancer accounts for 15–20% of all breast cancer cases. Although the development of monoclonal antibodies (e.g., trastuzumab, pertuzumab), tyrosine kinase inhibitors (e.g., lapatinib, pyrotinib), and antibody-drug conjugates (e.g., T-DM1, trastuzumab deruxtecan) has greatly improved patient prognosis, primary or acquired resistance to anti-HER2 therapy remains a major clinical challenge, leading to treatment failure and disease progression. Recent research has elucidated diverse resistance mechanisms, including HER2 signaling pathway aberrations (such as receptor mutations, alternative splicing, and bypass activation), tumor microenvironment remodeling (involving immunosuppressive cells, metabolic reprogramming, and immune checkpoint molecules), and ADC-specific resistance (impaired internalization,… More >

Tingting Yang¹, Meng Guan¹, Xin Guan¹, Lihua Kang¹, Xiaomeng Wang¹, Yanjie Guan¹, Yang Yang², Wei Deng³, Guoxiang Wang^1,*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.083563 - 16 July 2026

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 >

Juan Wu^1,2, Yue Wang³, Honglin Yan¹, Juanjuan Li², Chuntao Quan^4,*, Jingping Yuan^1,*, Shengrong Sun^2,*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.081653 - 16 July 2026

Abstract Objectives: Despite the success of CDK4/6 inhibitors (CDK4/6i) in treating HR+/HER2- breast cancer (BC), some patients experience treatment failure due to CDK4/6i resistance. This study aimed to investigate whether targeting Aurora A kinase enhances CDK4/6 inhibitor sensitivity. Methods: An Abemaciclib-resistant cell line (MCF7AR) was developed by treating MCF7 cells with gradually increasing concentrations of Abemaciclib. We evaluated the relative protein levels of p-RB, p-Aurora A, Aurora A, and USP22 in cell cultures, animal tissues, and clinical samples. The effect of Aurora A inhibition on reversing CDK4/6i resistance was assessed using cell viability assays and tumor… More >

Zhihao Wei^1,#, Jijie Cai^1,#, Sifen Wang^2,#, Yachen Li³, Libo Luo¹, Jun Chen¹, Fuyu Li¹, Hongyu Nie¹, Ke Gong^4,*, Manbo Cai^1,*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.079281 - 16 July 2026

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 >

Jia Liu^1,2,#, Binqian Wang^1,#, Yannan Jin¹, Wenquan Chen¹, Ruohan Shi¹, Weijia Wang¹, Xiaojing Zhang¹, Yi Tan³, Zhongran Man³, Bo Hu¹, Lisen Zhu¹, Biao Zhang^3,*, Chongchan Bao^4,5,*, Gongsheng Jin^1,*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.079137 - 16 July 2026

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 >

Yen-Dun Tony Tzeng^1,2,#, Chen-Yueh Wen^3,4,#, Su-Boon Yong^5,6, Zhi-Hong Wen^7,8, An-Jen Chiang^9,*, Chia-Jung Li^8,10,11,12,*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.078924 - 16 July 2026

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

Wei Lee¹, Hung-Yu Lin^1,2,*, Pei-Yi Chu^1,3,*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.078813 - 16 July 2026

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 >

Ching-Chun Ho¹, Yen-Cheng Chen^1,2, Wei-Liang Lean¹, Wen-Sheng Wu^1,*

Oncology Research, Vol.34, No.8, 2026, DOI:10.32604/or.2026.077693 - 16 July 2026

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 >

Hsing-Ju Wu^1,2, Yu-Chieh Tsai^3,*, Hung-Yu Lin^2,4,*

European Cytokine Network, Vol.37, No.2, pp. 121-135, 2026, DOI:10.32604/ecn.2026.079012 - 30 June 2026

Abstract Backgrounds: Lymph node metastasis is a critical determinant of breast cancer prognosis, yet the specific microenvironmental cytokines driving this process remain elusive. This study aims to identify key prognostic cytokines linking nodal metastasis to tumor microenvironment (TME) remodeling and to evaluate their clinical utility. Methods: A predefined panel of 176 microenvironmental genes was evaluated using differential expression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm on the TCGA-BRCA cohort to identify optimal predictors of nodal metastasis. Prognostic value was assessed via Kaplan-Meier, subgroup, and multivariate Cox regression analyses, and validated across five… More > Graphic Abstract

Raquel Sanchez-Baltasar¹, Nerea Castañeda-Fernández¹, Jorge Olivares-Arancibia², Carlos Torres-Villar^3,4, Julio Plaza-Diaz^5,6,7,8,*, Lourdes Herrera-Quintana^1,*

Oncology Research, Vol.34, No.7, 2026, DOI:10.32604/or.2026.081924 - 16 June 2026

Abstract Breast cancer (BC) is the most frequently diagnosed malignancy in women worldwide and remains one of the leading causes of cancer-related mortality, with substantial international disparities in incidence, stage at diagnosis, access to treatment, and survival. In recent years, BC management has evolved rapidly through advances in molecular characterization, imaging, pathology, targeted therapies, immunotherapy, and survivorship care. Nevertheless, important gaps persist in early and accurate detection, biomarker standardization, equitable access to care, and patient-specific treatment selection. These advances require timely, evidence-based, and context-specific clinical frameworks to support appropriate implementation, and to avoid the use of… More >