Xiangnan Feng^1,#, Dayong Li^2,#, Pingyu Wang¹, Xinyu Li², Guangyao Li^2,*

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 >

Chiao-Ping Chen^1,2, Yan-Jei Tang^1,2, You-Yan Cai¹, Yi-Ru Pan³, Chun-Nan Yeh^3,4, Wen-Kuan Huang^1,2, Chih-Hong Lo^1,2, Yu-Tien Hsiao^1,2, Hsuan-Jen Shih^1,*, Chiao-En Wu^1,2,4,5,*

Oncology Research, Vol.33, No.11, pp. 3429-3446, 2025, DOI:10.32604/or.2025.066672 - 22 October 2025

Abstract Background: KIT proto-oncogene, receptor tyrosine kinase (KIT, CD117) and platelet-derived growth factor-alpha (PDGFRA) are key drivers of gastrointestinal stromal tumors (GIST), but resistance to targeted therapy often arises from tumor protein p53 (p53) alterations and loss of cell cycle control. However, the role of p53 status in GIST therapeutic potential has rarely been studied, so this study aimed to employ both wild-type and mutant p53 GIST models to investigate how p53 dysfunction influences the efficacy of p53 pathway-targeted therapies. Methods: The efficacy of the mouse double minute 2 homolog (MDM2) inhibitor (HDM201) and the Wee1… More >

Jun Li¹, Kangmin Yu¹, Zhiyong Chen¹, Dan Xing², Binshan Zha¹, Wentao Xie¹, Huan Ouyang¹, Changjun Yu^3,*

Oncology Research, Vol.33, No.11, pp. 3469-3492, 2025, DOI:10.32604/or.2025.066193 - 22 October 2025

Abstract Objectives: Colorectal cancer (CRC) remains a major contributor to global cancer mortality, ranking second worldwide for cancer-related deaths in 2022, and is characterized by marked heterogeneity in prognosis and therapeutic response. We sought to construct a machine-learning prognostic model based on a complement-related risk signature (CRRS) and to situate this signature within the CRC immune microenvironment. Methods: Transcriptomic profiles with matched clinical annotations from TCGA and GEO CRC cohorts were analyzed. Prognostic CRRS genes were screened using Cox proportional hazards modeling alongside machine-learning procedures. A random survival forest (RSF) predictor was trained and externally validated.… More >

Takeshi Toyozumi^1,*, Hideaki Shimada², Hisahiro Matsubara¹

Oncology Research, Vol.33, No.11, pp. 3185-3206, 2025, DOI:10.32604/or.2025.065818 - 22 October 2025

Abstract Cancer immunotherapy has long been established as an important treatment option for cancers. In particular, Immune Checkpoint Inhibitor (ICI) has been reported to be effective against various gastrointestinal cancers (esophageal cancer, gastric cancer, colorectal cancer); however, the treatment phase in which ICI should be used and how it should be incorporated into the treatment strategy vary depending on the cancer type being treated. Multiple clinical trials and basic research on ICIs are currently underway, and new insights from these results will continue to change the clinical treatment strategy of gastrointestinal cancers. While it is desirable… More >

Sudhakar Tummala^1,2,*, Sajjad Hussain Chauhdary³, Vikash Singh⁴, Roshan Kumar⁵, Seifedine Kadry⁶, Jungeun Kim^7,*

CMES-Computer Modeling in Engineering & Sciences, Vol.144, No.3, pp. 3585-3605, 2025, DOI:10.32604/cmes.2025.069731 - 30 September 2025

Abstract Lightweight deep learning models are increasingly required in resource-constrained environments such as mobile devices and the Internet of Medical Things (IoMT). Multi-head convolution with channel attention can facilitate learning activations relevant to different kernel sizes within a multi-head convolutional layer. Therefore, this study investigates the capability of novel lightweight models incorporating residual multi-head convolution with channel attention (ResMHCNN) blocks to classify medical images. We introduced three novel lightweight deep learning models (BT-Net, LCC-Net, and BC-Net) utilizing the ResMHCNN block as their backbone. These models were cross-validated and tested on three publicly available medical image datasets:… More >

Mingyang Tang^1,2,#, Shengfu He^3,#, Bao Meng^1,2, Qingyue Zhang^1,2, Chengcheng Li^1,2, Yating Sun^1,2, Weijie Sun^1,2, Cui Wang⁴, Qingxiang Kong⁵, Yanyan Liu^1,2, Lifen Hu^1,2, Yufeng Gao^1,2, Qinxiu Xie^1,2, Jiabin Li^1,2,*, Ting Wu^1,2,*

Oncology Research, Vol.33, No.10, pp. 3077-3100, 2025, DOI:10.32604/or.2025.067065 - 26 September 2025

Abstract Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths. The Nod-like receptor (NLR) family is involved in innate immunity and tumor progression, but its role in HCC remains unclear. This study aimed to evaluate the prognostic value and biological function of NLR genes in HCC. Methods: Transcriptomic and clinical data from The Cancer Genome Atlas were analyzed using nonnegative matrix factorization (NMF) to classify HCC into molecular subtypes. Differentially expressed genes were used to build an NLR-based prognostic model (NLR_score) through univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox… More > Graphic Abstract

Xinyao Huang^1,#, Renjun Gu^2,3,#, Ziyun Li^4,*, Fangyu Wang^3,*

Oncology Research, Vol.33, No.10, pp. 2857-2902, 2025, DOI:10.32604/or.2025.066805 - 26 September 2025

Abstract Cold tumors, defined by insufficient immune cell infiltration and a highly immunosuppressive tumor microenvironment (TME), exhibit limited responsiveness to conventional immunotherapies. This review systematically summarizes the mechanisms of immune evasion and the therapeutic strategies for cold tumors as revealed by multi-omics technologies. By integrating genomic, transcriptomic, proteomic, metabolomic, and spatial multi-omics data, the review elucidates key immune evasion mechanisms, including activation of the WNT/β-catenin pathway, transforming growth factor-β (TGF-β)–mediated immunosuppression, metabolic reprogramming (e.g., lactate accumulation), and aberrant expression of immune checkpoint molecules. Furthermore, this review proposes multi-dimensional therapeutic strategies, such as targeting immunosuppressive pathways (e.g.,… More > Graphic Abstract

Rosa Scarpitta^1,#, Emiliano Cappello^1,#, Alice Cangialosi¹, Veronica Gori¹, Giulia De Luca^1,2, Giovanni Gori³, Guido Bocci^1,*

Oncology Research, Vol.33, No.10, pp. 2603-2656, 2025, DOI:10.32604/or.2025.066260 - 26 September 2025

Abstract Central nervous system (CNS) tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-related mortality. Their rarity compared to adult cancers has made enrolling sufficient cases for clinical trials challenging. Consequently, pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics. This review examines key aspects of phase I pediatric oncology trials, including study design, primary outcomes, and pharmacological approaches, along with secondary considerations like clinical responses and ethical aspects. Firstly, we evaluated all phase I trial protocols focusing on pediatric CNS tumors… More > Graphic Abstract

Eleni Kokkotou^*, Andriani Charpidou, Nikolaos Syrigos

Oncology Research, Vol.33, No.10, pp. 2657-2672, 2025, DOI:10.32604/or.2025.066228 - 26 September 2025

Abstract Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) serve an essential role in tumor angiogenesis and have emerged as potential therapeutic targets in lung cancer. This review explores the significance of serum VEGF levels as a predictive biomarker in non-small cell lung cancer (NSCLC). The VEGF family, consisting of VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor (PlGF), engages with specific receptors, including tyrosine kinase receptors (VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilin receptors (NRP-1 and NRP-2), to promote angiogenesis and lymphangiogenesis. VEGF-A, the primary component of the VEGF family, binds to VEGFR-2 to stimulate… More >

Ting Wei^1,2,#, Pengli Wei^2,3,#, Yalei Wang^1,2, Yaqiu Mao^2,3, Jian Yan², Xiaotong Hu², Zhenze Qi², Xu Cai², Changkai Jia², Zhiyuan Zhao², Bingkun Li², Min Qiao², Yaxin Zou^2,3, Tingting Yang⁴, Shiyang Sun², Xuesong Feng³, Pengyun Li^2,*, Hongzhou Shang^1,*, Zhibing Zheng²

Oncology Research, Vol.33, No.10, pp. 2981-3006, 2025, DOI:10.32604/or.2025.065123 - 26 September 2025

Abstract Objectives: Immunomodulatory drugs (IMiDs), functioning as molecular glue degraders, have been approved for treating various hematological malignancies; however, the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment. The study aimed to develop degraders with potent efficiency and low toxicity. Methods: Phenotypic profiling, elaborate structure-activity relationships (SAR), rational drug design and degradation profiles investigations, quantitative proteomics analysis and cell-based functional studies, and pharmacokinetic studies were conducted to develop more potent degraders. Results: This study developed novel CRBN-binding moieties through methylene deletion in lenalidomide’s isoindole core. Lead… More > Graphic Abstract