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  • 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

  • Open Access

    ARTICLE

    SORBS1 Knockdown Resists S/G2 Arrest and Apoptosis Caused by Polyphyllin H-Induced DNA Damage in Pancreatic Cancer

    Xinxin Hu1,2,#, Yuye Xue3,#, Fei Fang4, Jie Li2, Xiaofeng Yuan2, Guang Cheng5, Hailong Yuan3, Yongqiang Zhang2, Yuefei Zhou5, Shuangwu Yang5, Pengcheng Qiu2,*, Yunyang Lu2, Haifeng Tang2,*

    Oncology Research, Vol.33, No.9, pp. 2491-2506, 2025, DOI:10.32604/or.2025.064454 - 28 August 2025

    Abstract Objectives: The Sorbin and SH3 domain containing 1 (SORBS1), a protein linked to insulin signaling CBL interaction, was investigated for its role in pancreatic cancer apoptosis. This study explored polyphyllin H (PPH)’s ability to restore SORBS1-knockdown-mediated repair functions. Methods: PANC-1 cells were divided into Blank, overexpression (OE), and knockdown groups. CCK-8 assays assessed proliferation and drug toxicity. Western blot and flow cytometry analyzed SORBS1 levels and PPH effects. Comet assays quantified DNA damage. Subcutaneous xenograft tumors in nude mice (Blank vs. knockdown) were treated with PPH to evaluate in vivo efficacy. SORBS1-H2AX gene correlation was analyzed… More > Graphic Abstract

    SORBS1 Knockdown Resists S/G2 Arrest and Apoptosis Caused by Polyphyllin H-Induced DNA Damage in Pancreatic Cancer

  • Open Access

    REVIEW

    The impact of oxidative stress and the NRF2-KEAP1-ARE signaling pathway on anticancer drug resistance

    FLáVIA ALVES VERZA1,#,*, GUILHERME CARVALHO DA SILVA2,#, FELIPE GARCIA NISHIMURA2

    Oncology Research, Vol.33, No.8, pp. 1819-1834, 2025, DOI:10.32604/or.2025.065755 - 18 July 2025

    Abstract Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cancer development, progression, and resistance to therapy. The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1)-antioxidant response element (ARE) signaling pathway is central to maintaining redox balance by regulating the expression of antioxidant and detoxification genes. Under physiological conditions, this pathway protects cells from oxidative damage, however, sustained activation of NRF2 in cancer, often due to mutations in KEAP1, supports tumor cell survival, More > Graphic Abstract

    The impact of oxidative stress and the NRF2-KEAP1-ARE signaling pathway on anticancer drug resistance

  • Open Access

    REVIEW

    Non-coding RNAs as potential mediators of resistance to lung cancer immunotherapy and chemotherapy

    JIAHUI WANG1,#, HONGCHENG GE2,3,#, ZHENGYUAN YU1,*, LINGZHI WU1,*

    Oncology Research, Vol.33, No.5, pp. 1033-1054, 2025, DOI:10.32604/or.2024.058256 - 18 April 2025

    Abstract Lung cancer is a common cause of cancer-related death globally. The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy. However, as the treatment cycle progresses and the disease evolves, the emergence of acquired resistance leads to treatment failure. Many researches have shown that non-coding RNAs (ncRNAs) not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer, mediating drug resistance by regulating multiple targets and pathways. In addition, the regulation of immune response by ncRNAs is dualistic, forming a microenvironment for inhibits/promotes More >

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