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  • Open Access

    REVIEW

    Progression on Mechanism and Therapeutic Implications of Neddylation in Lung Cancer

    Jiayu Zou1,2,3, Yajie Lu3, Jiaqi Li3, Zhaokai Zhou4,5, Fu Peng3, Pu Qiu2,*, Hailin Tang6, Cheng Peng1,*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.071940 - 19 January 2026

    Abstract Lung cancer is the most common but fatal malignant tumor worldwide. Patients with lung cancer experienced a relatively low 5-year overall survival rate, and issues such as metastasis and drug resistance remain prominent challenges in its clinical management. Neddylation, a novel type of post-translational modification, was overactivated in lung cancer and was closely associated with its occurrence, development, metastasis, and drug resistance. This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation, metastasis, and drug resistance mechanisms, with a focus on More >

  • Open Access

    REVIEW

    Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies

    Min Hee Kim1, Boyoon Huh1, Joo-Won Park1,*, Woo-Jae Park2,*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.071523 - 19 January 2026

    Abstract Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors. Among various regulatory molecules, sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation, apoptosis, and metastasis through metabolic interconversions, including phosphorylation, glycosylation, and the generation of sphingosine-1-phosphate. This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression. Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites, such as sphingosine-1-phosphate, which collectively influence tumor growth More >

  • Open Access

    REVIEW

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

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

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

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

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

  • Open Access

    REVIEW

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

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

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

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

  • Open Access

    ARTICLE

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

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

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

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

  • Open Access

    REVIEW

    Molecular Mechanisms of Gemcitabine Resistance in Cholangiocarcinoma

    Sonexai Kidoikhammouan1, Charupong Saengboonmee2,3, Sopit Wongkham2,3, Wunchana Seubwai3,4,*

    Oncology Research, Vol.33, No.12, pp. 3679-3699, 2025, DOI:10.32604/or.2025.069027 - 27 November 2025

    Abstract Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelium. Surgical resection remains the primary curative treatment for CCA. However, most CCA patients are diagnosed at an advanced stage, which limits the applicability of surgical resection. Gemcitabine is widely used as a first-line chemotherapeutic agent for unresectable CCA. Its efficacy is often compromised by the development of drug resistance, which leads to poor clinical outcomes and low survival rates of CCA patients. At present, the mechanisms underlying gemcitabine resistance in CCA remain unclear. This review aimed to comprehensively summarize the current knowledge on the More >

  • Open Access

    ARTICLE

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

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

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

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

  • Open Access

    REVIEW

    Unraveling Immunotherapy Resistance in Solid Tumors: Decoding Mechanisms and Charting Future Therapeutic Landscapes

    Huan Wang1,#, Jindong Xie1,#, Na Li1, Qianwen Liu1, Wenqi Song1, Wenkuan Chen1, Cheng Peng2,*, Hailin Tang1,*

    Oncology Research, Vol.33, No.12, pp. 3789-3800, 2025, DOI:10.32604/or.2025.067592 - 27 November 2025

    Abstract Solid tumors comprise the majority of the global cancer burden, with their incidence and associated mortality posing considerable challenges to public health systems. With population growth and aging, the burden of these tumors is anticipated to increase further in the coming decades. The progression of solid tumors depends on dynamic interactions between malignantly transformed cells and the tumor microenvironment (TME). Immune checkpoint inhibitor therapy improves T cell-mediated antitumor activity by suppressing regulatory pathways, such as programmed cell death protein 1/programmed death-ligand 1. Nonetheless, its widespread application is constrained by drug resistance. In this comprehensive review, More >

  • Open Access

    REVIEW

    Lactylation in Cancer: Unlocking the Key to Drug Resistance and Therapeutic Breakthroughs

    Xiangnan Feng1,#, Dayong Li2,#, Pingyu Wang1, Xinyu Li2, Guangyao Li2,*

    Oncology Research, Vol.33, No.11, pp. 3327-3346, 2025, DOI:10.32604/or.2025.067343 - 22 October 2025

    Abstract Lactylation, a post-translational modification process that adds lactate groups to lysine residues, plays a crucial role in cancer biology, especially in drug resistance. However, the specific molecular mechanisms of lactylation in cancer progression and drug resistance are still unclear, and therapeutic strategies targeting the lactylation pathway are expected to overcome metabolic reprogramming and immune evasion. Therefore, this article provides a comprehensive description and summary of lactylation modification and tumor drug resistance. Numerous studies have shown that, due to the Warburg effect, there is an abnormally high level of lactate in tumor cells. Elevated levels of… More >

  • Open Access

    REVIEW

    Cancer 3D Models: Essential Tools for Understanding and Overcoming Drug Resistance

    Sofija Jovanović Stojanov1, Marija Grozdanić1, Mila Ljujić2, Sandra Dragičević2, Miodrag Dragoj1, Jelena Dinić1,*

    Oncology Research, Vol.33, No.10, pp. 2741-2785, 2025, DOI:10.32604/or.2025.067126 - 26 September 2025

    Abstract Anticancer drug resistance remains a major challenge in cancer treatment hindering the efficacy of chemotherapy and targeted therapies. Conventional two-dimensional (2D) cell cultures cannot replicate the complexity of the in vivo tumor microenvironment (TME), limiting their utility for drug resistance research. Therefore, three-dimensional (3D) tumor models have proven to be a promising alternative for investigating chemoresistance mechanisms. In this review, various cancer 3D models, including spheroids, organoids, scaffold-based models, and bioprinted models, are comprehensively evaluated with a focus on their application in drug resistance studies. We discuss the materials, properties, and advantages of each model, highlighting More > Graphic Abstract

    Cancer 3D Models: Essential Tools for Understanding and Overcoming Drug Resistance

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